Invasive Potential (invasive + potential)

Distribution by Scientific Domains


Selected Abstracts


2-Chloroadenosine modulates PAR-1 and IL-23 expression and enhances docetaxel effects on PC3 cells

THE PROSTATE, Issue 4 2008
Alba Minelli
Abstract BACKGROUND Docetaxel-based chemotherapy is the only treatment that demonstrated an overall survival benefit in men with hormone refractory prostate cancer. 2-CADO inhibits the growth of PC3 cells by inducing apoptosis and cell cycle arrest through a mechanism that involves cellular uptake. METHODS Androgen-independent and -sensitive (PC3 and LNCaP) prostate cancer cells and non-neoplastic HECV cells were used in the study. Proliferation and cell cycle progression were analyzed in the presence of 2-CADO and Docetaxel. Invasive potential was assessed by soft agar assay and metastatic ability by adhesion assay. IL-23 and PAR-1 expression were determined by real time PCR. RESULTS 2-CADO pre-treatment followed by Docetaxel at subclinical dosage reduced the viability of either PC3 or LNCaP while it did not enhance Docetaxel-induced cytotoxicity in adherent non-neoplastic HECV. The drugs reduced the invasive potential of PC3 cells by inducing apoptosis and blocking cell cycle progression in the S-phase. Down-regulation of PAR-1 gene expression resulted in a slightly lower metastatic potential, whereas up-regulation of IL-23 induced the activation of the immune system. CONCLUSIONS Pretreatment of PC3 cells with 2-CADO decreased the effective concentration of Docetaxel, lowered the metastatic potential, and induced the production of cytokines known to stimulate the immune response against cancer. The treatment was effective for prostate cancer cells independently on their androgen sensitiveness. Prostate 68: 360,372, 2008. 2008 Wiley-Liss, Inc. [source]


Rapid evolution in introduced species, ,invasive traits' and recipient communities: challenges for predicting invasive potential

DIVERSITY AND DISTRIBUTIONS, Issue 4 2008
Kenneth D. Whitney
ABSTRACT The damaging effects of invasive organisms have triggered the development of Invasive Species Predictive Schemes (ISPS). These schemes evaluate biological and historical characteristics of species and prioritize those that should be the focus of exclusion, quarantine, and/or control. However, it is not clear how commonly these schemes take microevolutionary considerations into account. We review the recent literature and find that rapid evolutionary changes are common during invasions. These evolutionary changes include rapid adaptation of invaders to new environments, effects of hybridization, and evolution in recipient communities. Strikingly, we document 38 species in which the specific traits commonly associated with invasive potential (e.g. growth rate, dispersal ability, generation time) have themselves undergone evolutionary change following introduction, in some cases over very short (, 10 year) timescales. In contrast, our review of 29 ISPS spanning plant, animal, and microbial taxa shows that the majority (76%) envision invading species and recipient communities as static entities. Those that incorporate evolutionary considerations do so in a limited way. Evolutionary change not only affects the predictive power of these schemes, but also complicates their evaluation. We argue that including the evolutionary potential of species and communities in ISPS is overdue, present several metrics related to evolutionary potential that could be incorporated in ISPS, and provide suggestions for further research on these metrics and their performance. Finally, we argue that the fact of evolutionary change during invasions begs for added caution during risk assessment. [source]


Feeding and breeding across host plants within a locality by the widespread thrips Frankliniella schultzei, and the invasive potential of polyphagous herbivores

DIVERSITY AND DISTRIBUTIONS, Issue 5 2000
M. Milne
Abstract. Polyphagous insect herbivores could be expected to perform relatively well in new areas because of their ability to exploit alternative resources. We investigated relative abundance patterns of the polyphagous thrips species Frankliniella schultzei, which is characteristically found on plants from many different families, to establish the role of different host plant species in a single locality where the species is not indigenous (Brisbane, south-eastern Queensland, Australia). F. schultzei females and larvae were always present in flowers (where oviposition takes place) and never on leaves of the eight plant species that we surveyed regularly over one year. They were present in flowers of Malvaviscus arboreus in much higher densities than for any other host. F. schultzei females were more fecund and larvae developed faster on floral tissue diets of M. arboreus than on those of other hosts. M. arboreus is therefore regarded as the ,primary' host plant of F. schultzei in the locality that we investigated. The other species are regarded as ,minor' hosts. Available evidence indicates a common geographical origin of F. schultzei and M. arboreus. F. schultzei may therefore be primarily adapted to M. arboreus. The flowers of the minor species on which F. schultzei is also found may coincidentally share some features of the primary host. Adult thrips may therefore accumulate on minor hosts and breed there, but to a lesser extent than on the primary host. The general implications for investigating polyphagous host relationships and interpreting the ecology of these species as generalist invaders are spelt out. [source]


The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2002
H.-G. Yu
Summary Background Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines. Materials and Methods After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry. Results ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression. Conclusion Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells. [source]


The biogeography of prediction error: why does the introduced range of the fire ant over-predict its native range?

GLOBAL ECOLOGY, Issue 1 2007
Matthew C. Fitzpatrick
ABSTRACT Aim, The use of species distribution models (SDMs) to predict biological invasions is a rapidly developing area of ecology. However, most studies investigating SDMs typically ignore prediction errors and instead focus on regions where native distributions correctly predict invaded ranges. We investigated the ecological significance of prediction errors using reciprocal comparisons between the predicted invaded and native range of the red imported fire ant (Solenopsis invicta) (hereafter called the fire ant). We questioned whether fire ants occupy similar environments in their native and introduced range, how the environments that fire ants occupy in their introduced range changed through time relative to their native range, and where fire ant propagules are likely to have originated. Location, We developed models for South America and the conterminous United States (US) of America. Methods, We developed models using the Genetic Algorithm for Rule-set Prediction (GARP) and 12 environmental layers. Occurrence data from the native range in South America were used to predict the introduced range in the US and vice versa. Further, time-series data recording the invasion of fire ants in the US were used to predict the native range. Results, Native range occurrences under-predicted the invasive potential of fire ants, whereas occurrence data from the US over-predicted the southern boundary of the native range. Secondly, introduced fire ants initially established in environments similar to those in their native range, but subsequently invaded harsher environments. Time-series data suggest that fire ant propagules originated near the southern limit of their native range. Conclusions, Our findings suggest that fire ants from a peripheral native population established in an environment similar to their native environment, and then ultimately expanded into environments in which they are not found in their native range. We argue that reciprocal comparisons between predicted native and invaded ranges will facilitate a better understanding of the biogeography of invasive and native species and of the role of SDMs in predicting future distributions. [source]


Short- and long-range dispersal of medfly, Ceratitis capitata (Dipt., Tephritidae), and its invasive potential

JOURNAL OF APPLIED ENTOMOLOGY, Issue 8 2007
A. Meats
Abstract:, Data were obtained from mark recapture trials pertaining to the dispersal of medfly, Ceratitis capitata (Dipt., Tephritidae), over both short (10,160 m) and very long distances (0.5,9.5 km) within the surveillance trapping array in Adelaide, Australia. They could be related to previously reported data sets by expressing the capture rates of each set in common terms that corrected for differences in recapture rate resulting from type of trap, season or climate. The mean capture rate at each distance from the point of release in each data set was expressed as a percentage of the real or inferred rate of that set at a distance of 100 m. The resulting distribution of dispersal distances conformed to both an inverse power model and a modified Cauchy model regardless of whether the present and previous data were combined or not. The modified Cauchy model inferred that the median distance flown was extremely short and 90% of flies displaced only 400,700 m despite the fact that a consistent trend in declining catch rates was obtained up to 9.5 km. The spread of invading propagules in quarantined zones in the first generation is likely to be limited by a decline to non-viable density within 1 km or less of the incursion point and the spread of larger infestations could be limited by the longevity of the dispersers. The results also have significance to the ability of surveillance trapping arrays to detect infestations and also to methods of distributing insects for the ,sterile insect technique'. [source]


Reduction of PKC, decreases cell proliferation, migration, and invasion of human malignant hepatocellular carcinoma

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2008
Trang-Tiau Wu
Abstract Protein kinase C (PKC) superfamily play key regulatory roles on the development of cancer. However, the exact role of these enzymes in human hepatocellular carcinoma (HCC) has not been well established. Using the RT-PCR and Western blotting to analyze the levels of PKC isoforms mRNA and protein in the five different differentiated hepatoma cell lines, we found that PKC, was highly expressed in the poor-differentiated HCC cell lines (SK-Hep-1 and HA22T/VGH) as compared with that in the well-differentiated HCC cell lines (PLC/PRF/5, Hep3B, and HepG2). When treated with PKC, antisense oligonucleotides (ODN), both HA22T/VGH and SK-Hep-1 cells lines showed the reduction of PKC, expression, as well as a deceleration in the growth rate and in the level of cyclin D1, but the increase in the levels of p53 and p21WAF1/CIP1. Moreover, the reduction of PKC, expression also inhibited the migratory and invasive potential of both HA22T/VGH and SK-Hep-1 cells lines, and revealed a down-regulation of several migration/invasion-related genes (MMP-1, u-PA, u-PAR, and FAK). These phenomenon were also confirmed by DNA-based small interfering RNA (siRNA) PKC, and PKC,/, specific inhibitor Go6976. Thus, the results indicated that PKC, may be associated with regulation of cell proliferation/migration/invasion in human poorly differentiated HCC cells, suggesting a role for the PKC, in the malignant progression of human HCC. J. Cell. Biochem. 103: 9,20, 2008. 2007 Wiley-Liss, Inc. [source]


siRNA mediated inhibition of MMP-1 reduces invasive potential of a human chondrosarcoma cell line

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005
Xiaoling Jiang
Matrix metalloproteinases (MMPs) play a crucial role in tumor cell invasion and metastasis. Expression of MMP-1 has been reported as a prognostic predictor of recurrence in human chondrosarcoma, and studies using human chondrosarcoma cell lines indicate that MMP-1 expression levels correlate with in vitro invasiveness. These observations suggest that MMP-1 activity has a central role in cell egress from the primary tumor at an early step in the metastatic cascade. In this study, siRNA was used to investigate whether knock down of the MMP-1 gene could be used to inhibit invasiveness in a human chondrosarcoma cell line. The inhibitory effect of siRNA on endogenous MMP-1 gene expression and protein synthesis was demonstrated via RT-PCR, Northern blotting, Western blotting, collagenase activity assay, and an in vitro cell migration assay. The siRNA inhibited MMP-1 expression specifically, since it did not affect the expression of endogenous glyceraldehyde phosphate dehydrogenase (GAPDH) nor other collagenases. Most importantly, the siRNA mediated reduction in MMP-1 expression correlated with a decreased ability of chondrosarcoma cells to invade a Type I collagen matrix. The reduction of invasive behavior demonstrated by human chondrosarcoma cells transfected with MMP-1 siRNA and the specificity of this inhibition supports the hypothesis that this metalloproteinase molecule is involved in initiation of chondrosarcoma metastasis. 2004 Wiley-Liss, Inc. [source]


Evidence for a combination of pre-adapted traits and rapid adaptive change in the invasive plant Centaurea stoebe

JOURNAL OF ECOLOGY, Issue 4 2010
Martin L. Henery
Summary 1. Introduced plants have the potential to rapidly evolve traits of ecological importance that may add to their innate potential to become invasive. During invasions, selection may favour genotypes that are already pre-adapted to conditions in the new habitat and, over time, alter the characteristics of subsequent generations. 2. Spotted knapweed (Centaurea stoebe) occurs in two predominantly spatially separated cytotypes in its native range (Europe,Western Asia), but currently only the tetraploid form has been confirmed in the introduced range (North America), where it is invasive. We used several common garden experiments to examine, across multiple populations, whether tetraploids and diploids from the native range differ in life cycle, leaf traits and reproductive capacity and if such differences would explain the predominance of tetraploids and their advance into new habitats in the introduced range. We also compared the same traits in tetraploids from the native and introduced range to determine whether any rapid adaptive changes had occurred since introduction that may have enhanced invasive potential of the species in North America. 3. We found tetraploids had lower specific leaf area, less lamina dissection and fewer, narrower leaves than diploids. Diploids exhibited a monocarpic life cycle and produced few if any accessory rosettes. Diploids produced significantly more seeds per capitulum and had more capitula per plant than tetraploids. In contrast, the vast majority of European tetraploids continued to flower in both seasons by regenerating from multiple secondary rosettes, demonstrating a predominantly polycarpic life cycle. 4. During early growth tetraploids from North America achieved greater biomass than both tetraploids and diploids from the native range but this did not manifest as larger above-ground biomass at maturity. In North American tetraploids there was also evidence of a shift towards a more strictly polycarpic life cycle, less leaf dissection, greater carbon investment per leaf, and greater seed production per capitulum. 5.,Synthesis. Our results suggest that the characteristics of tetraploid C. stoebe pre-adapted them (compared to diploid conspecifics) for spread and persistence of the species into habitats in North America characterized by a more continental climate. After the species' introduction, small but potentially important shifts in tetraploid biology have occurred that may have contributed significantly to successful invasion. [source]


Invasive mutualisms and the structure of plant,pollinator interactions in the temperate forests of north-west Patagonia, Argentina

JOURNAL OF ECOLOGY, Issue 1 2006
CAROLINA L. MORALES
Summary 1Alien species may form plant,animal mutualistic complexes that contribute to their invasive potential. Using multivariate techniques, we examined the structure of a plant,pollinator web comprising both alien and native plants and flower visitors in the temperate forests of north-west Patagonia, Argentina. Our main objective was to assess whether plant species origin (alien or native) influences the composition of flower visitor assemblages. We also examined the influence of other potential confounding intrinsic factors such as flower symmetry and colour, and extrinsic factors such as flowering time, site and habitat disturbance. 2Flowers of alien and native plant species were visited by a similar number of species and proportion of insects from different orders, but the composition of the assemblages of flower-visiting species differed between alien and native plants. 3The influence of plant species origin on the composition of flower visitor assemblages persisted after accounting for other significant factors such as flowering time, bearing red corollas, and habitat disturbance. This influence was at least in part determined by the fact that alien flower visitors were more closely associated with alien plants than with native plants. The main native flower visitors were, on average, equally associated with native and alien plant species. 4In spite of representing a minor fraction of total species richness (3.6% of all species), alien flower visitors accounted for > 20% of all individuals recorded on flowers. Thus, their high abundance could have a significant impact in terms of pollination. 5The mutualistic web of alien plants and flower-visiting insects is well integrated into the overall community-wide pollination web. However, in addition to their use of the native biota, invasive plants and flower visitors may benefit from differential interactions with their alien partners. The existence of these invader complexes could contribute to the spread of aliens into novel environments. [source]


Endoscopic resection of gastrointestinal lesions: Advancement in the application of endoscopic submucosal dissection

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2010
Abby Conlin
Abstract Curative endoscopic resection is now a viable option for a range of neoplastic lesions of the gastrointestinal tract (GIT) with low invasive potential. Risk of lymph node metastasis is the most important prognostic factor in selecting appropriate lesions for endoscopic therapy, and assessment of invasion depth is vital in this respect. To determine appropriate treatment, detailed endoscopic diagnosis and estimation of depth using magnifying chromoendoscopy is the gold standard in Japan. En bloc resection is the most desirable endoscopic therapy as risk of local recurrence is low and accurate histological diagnosis of invasion depth is possible. Endoscopic mucosal resection is established worldwide for the ablation of early neoplasms, but en bloc removal using this technique is limited to small lesions. Evidence suggests that a piecemeal resection technique has a higher local recurrence risk, therefore necessitating repeated surveillance endoscopy and further therapy. More advanced endoscopic techniques developed in Japan allow effective en bloc removal of early GIT neoplasms, regardless of size. This review discusses assessment of GIT lesions and options for endoscopic therapy with special reference to the introduction of endoscopic submucosal dissection into Western countries. [source]


Nm23-H1 promotes adhesion of CAL 27 cells in vitro

MOLECULAR CARCINOGENESIS, Issue 9 2009
ica Bago
Abstract nm23-H1 was found to diminish metastatic potential of carcinoma cell lines and therefore was placed in the group of metastatic suppressor genes. Its protein product has a function of a nucleoside diphosphate kinase (NDPK) as well as protein kinase and nuclease. Though it was found that Nm23-H1 is involved in many cellular processes, it is still not known how it promotes metastatic suppressor activity. Since the process of metastasis is dependent on adhesion properties of cells, the goal of our work was to describe the adhesion properties of CAL 27 cells (oral squamous cell carcinoma of the tongue) overexpressing FLAG/nm23-H1. In our experiments, cells overexpressing nm23-H1 show reduced migratory and invasive potential. Additionally, cells overexpressing nm23-H1 adhere stronger on substrates (collagen IV and fibronectin) and show more spread morphology than the control cells. Results obtained by EGF induction of migration revealed that the adhesion strength predetermined cell response to chemoattractant and that Nm23-H1, in this cell type, does not interfere with, EGF induced, Ras signaling pathway. These data contribute to the overall knowledge about nm23-H1 and its role in cell adhesion, migration, and invasion, especially in oral squamous cell carcinoma. 2009 Wiley-Liss, Inc. [source]


IL-1,, IL-1ra and IL-8 are differentially induced by Candida in experimental oral candidiasis

ORAL DISEASES, Issue 4 2007
JAMS Jayatilake
Objective:, To investigate the expression of interleukin-1, (IL-1,), IL-1ra and IL-8 by the oral epithelium challenged by various Candida species. Materials and methods:,In vitro candidiasis was induced by C. albicans wild type SC5314, its EFG1, CPH1 and secretory aspartyl proteinase (SAP) mutants and, ATCC isolates of C. albicans, C. tropicalis and C. dubliniensis using a reconstituted human oral epithelium (RHOE) model. IL-1,, IL-1ra and IL-8 levels in culture media were quantified by an enzyme-linked immunosorbent assay at 12, 24 and 48 h. Fungal invasion and IL-1ra expression in RHOE were detected by periodic acid-Schiff staining and immunohistochemistry. Results:, Overall, the invasive Candida induced relatively higher levels of IL-1,, IL-1ra and IL-8 in the culture media than the noninvasive isolates. IL-1, and IL-1ra levels induced by Candida with hyphal invasion were significantly higher (P < 0.05) than those induced by the isolates without hyphal invasion at 12, 24 and 48 h. Candida albicans SC5314 induced IL-1ra expression in RHOE at 12 and 24 h but not at 48 h consistent with its hyphal invasion; while the noninvasive mutants and non- albicans Candida induced IL-1ra expression at 48 h. Conclusions:, The cytokine expression profiles in experimental oral candidiasis may be associated with the invasive potential of Candida. [source]


2-Chloroadenosine modulates PAR-1 and IL-23 expression and enhances docetaxel effects on PC3 cells

THE PROSTATE, Issue 4 2008
Alba Minelli
Abstract BACKGROUND Docetaxel-based chemotherapy is the only treatment that demonstrated an overall survival benefit in men with hormone refractory prostate cancer. 2-CADO inhibits the growth of PC3 cells by inducing apoptosis and cell cycle arrest through a mechanism that involves cellular uptake. METHODS Androgen-independent and -sensitive (PC3 and LNCaP) prostate cancer cells and non-neoplastic HECV cells were used in the study. Proliferation and cell cycle progression were analyzed in the presence of 2-CADO and Docetaxel. Invasive potential was assessed by soft agar assay and metastatic ability by adhesion assay. IL-23 and PAR-1 expression were determined by real time PCR. RESULTS 2-CADO pre-treatment followed by Docetaxel at subclinical dosage reduced the viability of either PC3 or LNCaP while it did not enhance Docetaxel-induced cytotoxicity in adherent non-neoplastic HECV. The drugs reduced the invasive potential of PC3 cells by inducing apoptosis and blocking cell cycle progression in the S-phase. Down-regulation of PAR-1 gene expression resulted in a slightly lower metastatic potential, whereas up-regulation of IL-23 induced the activation of the immune system. CONCLUSIONS Pretreatment of PC3 cells with 2-CADO decreased the effective concentration of Docetaxel, lowered the metastatic potential, and induced the production of cytokines known to stimulate the immune response against cancer. The treatment was effective for prostate cancer cells independently on their androgen sensitiveness. Prostate 68: 360,372, 2008. 2008 Wiley-Liss, Inc. [source]


Establishment of a matrix-associated transepithelial resistance invasion assay to precisely measure the invasive potential of synovial fibroblasts

ARTHRITIS & RHEUMATISM, Issue 9 2009
Christina Wunrau
Objective Synovial fibroblasts (SFs) contribute to several aspects of the pathogenesis of rheumatoid arthritis (RA) and have been implicated most prominently in the progressive destruction of articular cartilage. Targeting the invasive phenotype of RASFs has therefore gained increasing attention, but the precise measurement of their invasive capacity and the evaluation of potential treatment effects constitute a challenge that needs to be addressed. This study used a novel in vitro invasion assay based on the breakdown of transepithelial electrical resistance to determine the course of fibroblast invasion into extracellular matrix. Methods A matrix-associated transepithelial resistance invasion (MATRIN) assay was used to assess SFs from patients with RA in comparison with SFs from patients with osteoarthritis (OA). The SFs were grown on a commercially available collagen mix that was placed onto the upper side of a Transwell polycarbonate membrane. In addition, freshly isolated cartilage extracts were studied to assess the conditions in vivo. Under this membrane, a monolayer of MDCK-C7 cells was seeded to create a high electrical resistance. Results Invasion of fibroblasts into the matrix affected the integrity of the MDCK-C7 monolayer and led to a measurable decrease and subsequent breakdown of electrical resistance. Unlike in the assay with OASFs, which did not achieve a breakdown of resistance up to 72 hours, RASFs exhibited a pronounced invasiveness in this assay, with a 50% breakdown after 42 hours. Treatment of fibroblasts with either a matrix metalloproteinase inhibitor or antibodies against ,1 integrin significantly reduced the invasiveness of RASFs. Conclusion The MATRIN assay is a valuable and sensitive biologic assay system that can be used to determine precisely the invasive potential of RASFs in vitro, and thus would be suitable for screening anti-invasion compounds. [source]


T-cadherin loss induces an invasive phenotype in human keratinocytes and squamous cell carcinoma (SCC) cells in vitro and is associated with malignant transformation of cutaneous SCC in vivo

BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2010
D. Pfaff
Summary Background, Cadherins play important roles in controlling keratinocyte growth, differentiation and survival. Atypical glycosylphosphatidylinositol-anchored T-cadherin (T-cad) is highly expressed in the basal keratinocyte layer of skin. The role of T-cad in keratinocyte biology and pathology is unclear. Objectives, To define the role of T-cad in the pathogenesis of cutaneous squamous cell carcinoma (SCC) through gain-of-function and loss-of-function studies in vitro and through examination of T-cad expression patterns in human cutaneous SCC specimens in relation to histological classification of degree of tumour differentiation. Methods,In vitro studies employed lentiviral-mediated overexpression/silencing of T-cad in normal human keratinocyte (HaCaT) and SCC (A431) cell lines, monolayer and multicellular spheroid culture models, cell morphology analyses and assays of random motility and invasion. Immunohistochemistry was performed on skin specimens from patients with actinic keratosis, Bowen disease or SCC. Results,In vitro, silencing of T-cad induced a morphologically elongated and disorganized cell phenotype, increased random motility and markedly enhanced invasive potential. Overexpression of T-cad induced a morphologically spread and compact cell phenotype and blunted invasive potential. In vivo, regional loss of T-cad expression was more frequent and prominent in SCC classified as moderately-to-poorly differentiated than in SCC classified as well differentiated. However, in both categories aberrant and/or absence of T-cad expression was associated with histological features of a potentially more malignant and invasive phenotype of cutaneous SCC. Conclusions, T-cad is a controlling determinant of SCC phenotype and invasive behaviour and its loss is associated with the process of malignant transformation from noninvasive to invasive SCC. [source]


P-cadherin expression reduced in squamous cell carcinoma of the oral cavity

CANCER, Issue 5 2005
An indicator of poor prognosis
Abstract BACKGROUND The loss of cadherin expression has been shown to correlate to the invasion and metastasis of many types of carcinomas. The purpose of the current study was to evaluate whether the impaired expression of E-cadherin (E-cad) and P-cadherin (P-cad) correlated with the clinical evolution and prognosis of oral squamous cell carcinoma (OSCC). METHODS The authors used immunohistochemical methods to analyze the expression pattern of E-cad and P-cad in healthy oral mucosa, in oral carcinoma in situ (CIS), and in surgical samples of 50 patients with the early stages (Stages I,II) of OSCC. RESULTS E-cad showed weak expression in the basal layer of the healthy oral mucosa and reduced expression in patients with oral CIS. P-cad expression was conserved on the basal and suprabasal layers of the healthy mucosa and, also, in the CIS. In the group of patients with OSCC, univariate analysis demonstrated that reduced expression of E-cad or P-cad correlated significantly with locoregional disease recurrence in the follow-up (P = 0.03 and P = 0.01, respectively). However, only the reduction in the expression of P-cad emerged as an independent prognostic marker in the multivariate analysis (P = 0.04, hazard ratio = 8.06). CONCLUSIONS These findings suggested that a decrease in E-cad and/or P-cad expression may contribute to the invasive potential of early OSCC. According to the current data, P-cad expression may be a potential independent prognostic factor in patients with OSCC. Cancer 2005. 2005 American Cancer Society. [source]


Hypoxia and low-nutrition double stress induces aggressiveness in a murine model of melanoma

CANCER SCIENCE, Issue 5 2009
Tsuyoshi Osawa
Antiangiogenic therapy is a potent cancer treatment, however, the possibility of recurrence and resistance to this approach remains. Here we show that hypoxia and low-nutrition double-deprivation stress induces reversible tumor aggressiveness. In a stress-cycle-dependent manner, murine melanoma cells showed morphological changes, up-regulated phospho-Akt, and abnormal regulation of multiple genes including fibroblast growth factor-21, a metabolic regulator, resulting in increased cell proliferation in vitro, and increased tumorigenesis and invasive potential in vivo. In this system, altered cellular metabolism participates in the adaptation of tumor to the double-deprivation stress. Our results suggest the targeting of a minor population of cancer cells resistant to both hypoxia and low nutrition to be an effective new antitumor strategy in combination with antiangiogenic therapy. (Cancer Sci 2009; 100: 844,851) [source]


Matrix metalloproteinase-2 expression in stromal tissues is a consistent prognostic factor in stage II colon cancer

CANCER SCIENCE, Issue 5 2009
Yoshiko Inafuku
For patients with stage II colon cancer, the usefulness of adjuvant chemotherapy remains controversial. Therefore, it is important to identify high-risk indicators. The biological prognostic factors for recurrence might allow further insight into the optimal treatment strategy for patients with node-negative disease. Matrix metalloproteinase-2 seems to be one of the essential factors for tumor invasion and lymph node metastasis. In this study, we analyzed the expression of cyclooxygenase-2 and matrix metalloproteinase-2 by immunohistochemical staining in 109 patients with stage II colon cancer. A positive correlation was observed between tumor cyclooxygenase-2 and tumor matrix metalloproteinase-2 expression (P = 0.0006) and between tumor cyclooxygenase-2 and stromal matrix metalloproteinase-2 expression (P < 0.0001). Stromal matrix metalloproteinase-2 expression was associated with disease-free survival (P = 0.0095) and was shown to be an independent risk factor for recurrence by multivariate analysis. In addition, we carried out an invasion assay in vitro to investigate whether cyclooxygenase-2 and matrix metalloproteinase-2 affected the tumor-invasive potential of colon cancer cell lines. The invasion assay showed that every cancer cell line acquired invasive potential in coculture with stromal cell lines and the cyclooxygenase-2 inhibitor suppressed this phenomenon by downregulating the matrix metalloproteinase-2 expression of stromal cells. In conclusion, these findings suggest that matrix metalloproteinase-2 expression in stromal cells can be a high-risk indicator for recurrence in patients with stage II colon cancer. (Cancer Sci 2009; 100: 852,858) [source]


Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell lines

INTERNATIONAL JOURNAL OF CANCER, Issue 10 2009
Shailesh Singh
Abstract Chemokines and chemokine receptors have been shown to be involved in metastatic process of prostate cancer (PCa). In this study, we show primary PCa tissues and cell lines (LNCaP and PC3) express CXCR5, a specific chemokine receptor for CXCL13. Expression of CXCR5 was significantly higher (p < 0.001) in PCa cases than compared to normal match (NM) tissues. CXCR5 intensity correlated (R2 = 0.97) with Gleason score. While prostate tumor tissues with Gleason scores , 7, displayed predominantly nuclear CXCR5 expression patterns, PCa specimens with Gleason scores , 6 showed predominantly membrane and cytoplasmic expression patterns that were comparable to benign prostatic hyperplasia (BPH). Similar to tissue expression, PCa cell lines expressed significantly more CXCR5 than normal prostatic epithelial cells (PrECs), and CXCR5 expression was distributed among intracellular and extracellular compartments. Functional in vitro assays showed higher migratory and invasive potentials toward CXCL13, an effect that was mediated by CXCR5. In both PCa cell lines, CXCL13 treatment increased the expression of collagenase-1 or matrix metalloproteinase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), stromelysin-2 (MMP-10) and stromelysin-3 (MMP-11). These data demonstrate the clinical and biological relevance of the CXCL13-CXCR5 pathway and its role in PCa cell invasion and migration. 2009 UICC [source]