Home About us Contact
|
Home About us Contact | ||
|
|
||
Invasive Growth (invasive + growth)
Selected AbstractsPhenotypic diversity of Flo protein family-mediated adhesion in Saccharomyces cerevisiaeFEMS YEAST RESEARCH, Issue 2 2009Sebastiaan E. Van Mulders Abstract The Saccharomyces cerevisiae genome encodes a Flo (flocculin) adhesin family responsible for cell,cell and cell,surface adherence. In commonly used laboratory strains, these FLO genes are transcriptionally silent, because of a nonsense mutation in the transcriptional activator FLO8, concealing the potential phenotypic diversity of fungal adhesion. Here, we analyse the distinct adhesion characteristics conferred by each of the five FLO genes in the S288C strain and compare these phenotypes with a strain containing a functional copy of FLO8. Our results show that four FLO genes confer flocculation, but with divergent characteristics such as binding strength, carbohydrate recognition and floc size. Adhesion to agar surfaces, on the other hand, largely depended on two adhesins, Flo10 and Flo11. Expression of any FLO gene caused a significant increase in cell wall hydrophobicity. Nevertheless, the capacity to adhere to plastic surfaces, which is believed to depend on hydrophobic interactions, differed strongly between the adhesins. Restoring Flo8 yielded both flocculation and cell,surface adherence, such as invasive growth, a phenotype not observed when any of the single FLO genes was overexpressed. Taken together, this study reveals how S. cerevisiae carries a small reservoir of FLO genes that allows cells to display a wide variety of adhesive properties. [source] Dickkopf-1 is overexpressed in human pancreatic ductal adenocarcinoma cells and is involved in invasive growthINTERNATIONAL JOURNAL OF CANCER, Issue 7 2010Nobuyasu Takahashi Abstract The protein products of the Dickkopf (DKK) genes are antagonists of Wnt glycoproteins, which participate in tumor development and progression by binding to frizzled receptors. In this study, the expression of DKK-1 was analyzed in a panel of 43 human cultured carcinoma cell lines. DKK-1 expression was consistently and significantly upregulated in pancreatic carcinoma cell lines. Low level of DKK-3 expression was also seen. In contrast, the expression of DKK-2 and -4 was not detectable in most pancreatic carcinoma cell lines. The overexpression of DKK-1 was confirmed in surgically resected human pancreatic cancer tissues, in which the mRNA level was evaluated in paired samples from cancerous and noncancerous pancreatic tissues. In ductal adenocarcinomas (23 cases), DKK-1 mRNA levels were significantly upregulated compared to corresponding noncancerous tissues in a statistically significant level. To test the biological role of DKK-1 in pancreatic carcinoma cells, we performed a knockdown of DKK-1 in SUIT-2 human pancreatic adenocarcinoma cell line and S2-CP8, its metastatic subline, using a retroviral short hairpin RNA expression vector. DKK-1 knockdown resulted in reduced migratory activity of SUIT-2 in vitro. The in vitro growth rate and Matrigel invasion were also suppressed by DKK-1 knockdown in S2-CP8 cells. Collectively, the evidence suggests that, despite of its presumed antagonistic role in Wnt signaling, DKK-1 may have a role in the aggressiveness of pancreatic carcinoma cells and could, therefore, serve as a novel biomarker of pancreatic cancer. [source] Distinct progression-associated expression of tumor and stromal MMPs in HaCaT skin SCCs correlates with onset of invasionINTERNATIONAL JOURNAL OF CANCER, Issue 10 2009Silvia Vosseler Abstract Matrix metalloproteinases (MMPs) are critically involved in tumor invasion and metastasis. However, failure of broad spectrum MMP inhibitors in clinical trials emphasizes the need for detailed analyses of the specific role of different MMPs in tumor malignancy. Using HaCaT-keratinocyte clones representing distinct stages in skin squamous cell carcinoma (SCC) progression, we demonstrate the expression of specific tumor and stroma-derived MMPs with the onset and maintenance of tumor invasion. Although MMP-9-positive leukocytes are present in benign and malignant tumor transplants at the onset of stromal activation and angiogenesis, mRNA expression of stroma-derived MMP-9 as well as MMP-2, ,13 and ,14 is exclusively found in enhanced malignant tumor transplants. Their expression initiates with the onset of invasion, whereas being absent in early noninvasive stages of malignant transplants. In addition, a high expression of tumor-derived MMP-1, ,2 and ,14 contributes to malignant and invasive tumor growth. However, stroma-derived MMP-3 is exclusively restricted to very late-stage invasive and malignant transplants. The functional contribution of these proteases to invasive growth is supported by the gelatinolytic activity in the tumor transplants that again initiates with the onset of invasive growth suggesting a crucial role of MMP-2, ,9, ,13 and ,14 for the establishment of a reactive stroma that promotes tumor invasion. These data demonstrate a complex cooperation of distinct tumor and stroma-derived MMPs in the establishment of malignant tumors and provide the basis for a more specific use of highly selective MMP inhibitors during distinct stages of tumor progression. © 2009 UICC [source] Noggin blocks invasive growth of murine B16-F1 melanoma cells in the optic cup of the chick embryo,,INTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Christian Busch Abstract Melanoma cells originate from the neural crest and are characterized by high migratory potential and invasive growth. After transplantation into the neural tube of the chick embryo, melanoma cells spontaneously emigrate along the neural crest pathways without tumor formation or malignant growth. This emigration depends on the constitutive over-expression of bone morphogenetic protein-2 (BMP-2) and can be ablated by the BMP-antagonist noggin. When transplanted into the embryonic optic cup, melanoma cells invade the host tissue and form malignant tumors. Here, we asked if the invasive growth of melanoma cells in the optic cup could be influenced by BMP-2 or noggin. Mouse B16-F1 cells were grown as aggregates, treated with BMP-2 or noggin during aggregation and transplanted into the optic cup of 3-day chick embryos. After 3 days of subsequent incubation, embryos were evaluated for melanoma cell invasiveness. Immunohistochemical examination revealed that untreated and BMP-2-treated melanoma cells had grown malignantly into the host tissue. However, noggin pretreatment of the aggregates had blocked melanoma cell invasiveness and tumor formation. We conclude that invasive growth of melanoma cells in vivo is BMP-dependent and can be ablated by noggin, thus rendering noggin a promising agent for the treatment of BMP-over-expressing melanoma. © 2007 Wiley-Liss, Inc. [source] Distribution of muscarinic receptor subtype M3 in melanomas and their metastasesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2008Matthias Oppitz Background:, Muscarinic acetylcholine receptors (mR) are involved in the regulation of cancer cell motility and cancer progression. mR have been shown in melanoma cell lines and cryostat sections of melanomas. To substantiate the experimental data, here the correlation of mR-expression with invasive growth was studied on the cellular level by comparison with HMB-45 immunoreactivity. Methods:, mR were detected by a M3 subtype-specific polyclonal antibody in normal skin, benign compound nevi, primary melanomas [nodular type, nodular malignant melanoma (NMM)] and metastases, and were compared with HMB-45 staining in parallel paraffin sections. Results:, The general staining pattern of anti-M3 and HMB-45 was similar with accentuation of zones with infiltrative growth. On the cellular level, only a subpopulation of the HMB-45 positive melanoma cells expressed mR. Immunoreactivity was encountered in 3 of 15 nevi, in 9 of 14 NMM and in 10 of 14 melanoma metastases. Polymorphonuclear granulocytes also exhibited strong reactivity for anti-M3. Conclusion:, mR-expression is associated with invasive migration of melanomas. [source] Factors influencing the incidence and prognosis of canine mammary tumoursJOURNAL OF SMALL ANIMAL PRACTICE, Issue 7 2000M. D. Perez Alenza Factors relating to the incidence of canine mammary tumours are reviewed. Increased age, intact status or ovariectomy after 2.5 years of age, as well as progestagen treatment, can all lead to an increased risk of mammary neoplasia in the bitch. In addition, obesity early in life, and a habitual diet based on home-made food (rich in beef and pork, and poor in chicken) as opposed to commercial food, are also associated with the occurrence of mammary tumours. Other aspects related to incidence are also discussed. Increased age at diagnosis, invasive growth (fixed to adjacent tissues), large tumour size, ulceration of skin, and axillary or inguinal node involvement are clinical parameters associated with a low chance of survival after surgical excision of mammary tumours. Histological typing and grading of the tumour allows the establishment of a prognosis, which is poor where there is tumour proliferation as measured by S-phase fraction determination and Ki-67 immunostaining. [source] Mss11p is a transcription factor regulating pseudohyphal differentiation, invasive growth and starch metabolism in Saccharomyces cerevisiae in response to nutrient availabilityMOLECULAR MICROBIOLOGY, Issue 1 2003Marco Gagiano Summary In Saccharomyces cerevisiae, the cell surface protein, Muc1p, was shown to be critical for invasive growth and pseudohyphal differentiation. The transcription of MUC1 and of the co-regulated STA2 glucoamylase gene is controlled by the interplay of a multitude of regulators, including Ste12p, Tec1p, Flo8p, Msn1p and Mss11p. Genetic analysis suggests that Mss11p plays an essential role in this regulatory process and that it functions at the convergence of at least two signalling cascades, the filamentous growth MAPK cascade and the cAMP-PKA pathway. Despite this central role in the control of filamentous growth and starch metabolism, the exact molecular function of Mss11p is unknown. We subjected Mss11p to a detailed molecular analysis and report here on its role in transcriptional regulation, as well as on the identification of specific domains required to confer transcriptional activation in response to nutritional signals. We show that Mss11p contains two independent transactivation domains, one of which is a highly conserved sequence that is found in several proteins with unidentified function in mammalian and invertebrate organisms. We also identify conserved amino acids that are required for the activation function. [source] Characterisation of the CipC-like protein AFUA_5G09330 of the opportunistic human pathogenic mould Aspergillus fumigatusMYCOSES, Issue 4 2010Bettina Bauer Summary,Aspergillus fumigatus is currently the major airborne fungal pathogen that menaces immunocompromised individuals. Germination of inhaled conidia is a hallmark of the early infection process, but little is known about the underlying mechanisms. The intention of our ongoing studies is the identification of A. fumigatus proteins that are differentially expressed during germination and may provide insights in the germination process. Using a proteomic approach, we identified AFUA_5G09330 as a major hyphal-specific protein. This result was confirmed using monoclonal antibodies generated in this study. AFUA_5G09330 belongs to a fungal-specific protein family. The eponymous CipC protein of A. nidulans has been shown to be induced by concanamycin A, and transcriptional data from Cryptococcus neoformans demonstrate a strong up-regulation of the expression of a homologous gene during infection. Our data provide evidence that AFUA_5G09330 is a monomeric, cytoplasmic protein. We found no evidence for an overexpression of AFUA_5G09330 induced by concanamycin A or other stress conditions. AFUA_5G09330 is exclusively found in the hyphal morphotype that enables an invasive growth of A. fumigatus during infection. Further studies are required to define the biological function of this hyphae-specific protein and its potential relevance for the pathogenicity of A. fumigatus. [source] Effects of repeated low-dose UVB irradiation on the hyphal growth of Candida albicansMYCOSES, Issue 1 2006J. Brasch Summary Ultraviolet B light (UVB) can have negative phototropic effects on fungi. Candida albicans is often found on human skin exposed to UVB. Therefore, it is of medical interest to know whether a negative phototropic response to UVB irradiation can support an invasive growth of this potentially dangerous agent. In our study we investigated how repeated irradiation with low doses of UVB can influence the hyphal growth of C. albicans. Six randomly chosen strains of C. albicans were tested. Formation of hyphae was induced and maintained within transparent agar plates. The fungi were exposed to UVB three times daily for 7 days from either the obverse or the reverse side during incubation. The wavelength spectrum was in the range of 310,315 nm, single doses were between 0.0018 and 0.432 J cm,2. After 7 days the morphology and growth direction of C. albicans cells were determined microscopically. All six strains showed a common and dose-dependent response to UVB irradiation: the progression of hyphal growth was inhibited, no phototropic effects were seen and as a new finding an increased formation of blastospores was observed. We conclude that an irradiation of human skin colonized by C. albicans with doses of UVB that can occur under natural or artificial conditions is unlikely to trigger skin invasion by C. albicans. [source] Down-regulation of myeloid cell leukemia 1 by epigallocatechin-3-gallate sensitizes rheumatoid arthritis synovial fibroblasts to tumor necrosis factor ,,induced apoptosisARTHRITIS & RHEUMATISM, Issue 5 2009Salahuddin Ahmed Objective Overexpression of the antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) in rheumatoid arthritis (RA) synovial fibroblasts is a major cause of their resistance to tumor necrosis factor , (TNF,),induced apoptosis. This study was undertaken to evaluate the efficacy of epigallocatechin-3-gallate (EGCG) in down-regulating Mcl-1 expression and its mechanism of RA synovial fibroblast sensitization to TNF,-induced apoptosis. Methods EGCG effects on cultured RA synovial fibroblast cell morphology, proliferation, and viability over 72 hours were determined by microscopy and a fluorescent cell enumeration assay. Caspase 3 activity was determined by a colorimetric assay. Western blotting was used to evaluate the apoptosis mediators poly(ADP-ribose) polymerase (PARP), Mcl-1, Bcl-2, Akt, and nuclear translocation of NF-,B. Results In RA synovial fibroblasts, EGCG (5,50 ,M) inhibited constitutive and TNF,-induced Mcl-1 protein expression in a concentration- and time-dependent manner (P < 0.05). Importantly, EGCG specifically abrogated Mcl-1 expression in RA synovial fibroblasts and affected Mcl-1 expression to a lesser extent in osteoarthritis and normal synovial fibroblasts or endothelial cells. Inhibition of Mcl-1 by EGCG triggered caspase 3 activity in RA synovial fibroblasts, which was mediated via down-regulation of the TNF,-induced Akt and NF-,B pathways. Caspase 3 activation by EGCG also suppressed RA synovial fibroblast growth, and this effect was mimicked by Akt and NF-,B inhibitors. Interestingly, Mcl-1 degradation by EGCG sensitized RA synovial fibroblasts to TNF,-induced PARP cleavage and apoptotic cell death. Conclusion Our findings indicate that EGCG itself induces apoptosis and further sensitizes RA synovial fibroblasts to TNF,-induced apoptosis by specifically blocking Mcl-1 expression and, hence, may be of promising adjunct therapeutic value in regulating the invasive growth of synovial fibroblasts in RA. [source] Expression of Integrin ,v,3 in Gliomas Correlates with Tumor Grade and Is not Restricted to Tumor VasculatureBRAIN PATHOLOGY, Issue 3 2008Oliver Schnell MD Abstract In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of ,v,3 integrin caused by malignancy. The aim of our study was to assess the extent and pattern of ,v,3 integrin expression within primary glioblastomas (GBMs) compared with low-grade gliomas (LGGs). Tumor samples were immunostained for the detection of ,v,3 integrin and quantified by an imaging software. The expression of ,v,3 was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only. Subsequent analysis revealed that not only endothelial cells but also, to a large extent, glial tumor cells contribute to the overall amount of ,v,3 integrin in the tumors. To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the ,3 integrin subunit between GBMs and LGGs. The presented data lead to new insights in the pattern of ,v,3 integrin in gliomas and are of relevance for the inhibition of ,v,3 integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth. [source] A 5-decade analysis of 13,715 carcinoid tumorsCANCER, Issue 4 2003Irvin M. Modlin M.D., Ph.D. Abstract BACKGROUND Carcinoid tumors represent an unusual and complex disease spectrum with protean clinical manifestations. This compilation of several large United States-based databases comprising patients from 1950 to 1999 examines 13,715 carcinoid tumors and provides epidemiologic information regarding the natural history and evolution of the detection and diagnosis of this entity. METHODS The authors evaluated 10,878 carcinoid tumors that were identified by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) from 1973 to 1999 in addition to 2837 carcinoid tumors that were registered previously by two earlier NCI programs. To the authors' knowledge, this represents the largest current epidemiology series addressing carcinoid tumors to date. RESULTS Specific trends in incidence for carcinoid tumors of certain sites were identified. Among the most recently collected subset of data, sites that demonstrated the greatest incidence of carcinoids were the gastrointestinal tract (67.5%) and the bronchopulmonary system (25.3%). Within the gastrointestinal tract, most carcinoid tumors occurred in the small intestine (41.8%), rectum (27.4%), and stomach (8.7%). For all sites, age-adjusted incidence rates were highest in black males (4.48 per 100,000 population per year). Associated noncarcinoid tumors were frequent in conjunction with small intestinal (29.0%), gastric (20.5%), colonic (20.0%), and appendiceal (18.2%) carcinoids. The highest percentages of nonlocalized lesions were noted for cecal (81.5,83.2%) and pancreatic (71.9,81.3%) carcinoids, whereas the highest percentage of localized disease was found among rectal (81.7%), gastric (67.5%), and bronchopulmonary (65.4%) carcinoids. The best 5-year survival rates were recorded for patients with rectal (88.3%), bronchopulmonary (73.5%), and appendiceal (71.0%) carcinoids; these tumors exhibited invasive growth or metastatic spread in 3.9%, 27.5%, and 38.8% of patients, respectively. CONCLUSIONS Carcinoids appear to have increased in overall incidence over the past 30 years; for some sites, this trend has been evident for nearly half a century. Recent marked increases in gastric and rectal carcinoids and a concomitant decrease in appendiceal carcinoid incidence may be due in part to varying rules of registration among the compiled databases examined in this report or to improvements in diagnostic technology; increased awareness of and about carcinoid tumors also may play a significant role. In 12.9% of all patients with carcinoid, distant metastases already were evident at the time of diagnosis; the overall 5-year survival rate for all carcinoid tumors, regardless of site, was 67.2%. These findings bring into question the widely promulgated relative benignity of carcinoid disease. Certain carcinoid tumors, such as those of the rectum, appear to be over-represented among the black and Asian populations within the United States, suggesting the role of genetics in the development of this intriguing disease. Cancer 2003;97:934,59. © 2003 American Cancer Society. DOI 10.1002/cncr.11105 [source] Angiogenesis in patients with craniopharyngiomasCANCER, Issue 3 2002Correlation with treatment, outcome Abstract BACKGROUND Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that often exhibit aggressive and invasive growth. The authors hypothesized that tumor proliferation, spread, and recurrence are angiogenesis dependent and investigated the significance of vascularization relative to biologic behavior. To the authors' knowledge, angiogenesis for patients with craniopharyngiomas has not been examined to date. METHODS The authors measured microvessel densities in resected, histologically proven craniopharyngiomas using immunostains for CD-34, a monoclonal antibody that selectively recognizes endothelial cells. Both histologic types of craniopharyngiomas, adamantinomatous and papillary, were included in the study. In addition, the cellular distribution of vascular endothelial growth factor (VEGF), a strong stimulator of new vessel formation, was assessed by both immunohistochemistry and in situ hybridization for VEGF receptor 2 (VEGFR-2) mRNA expression. RESULTS Histologically, small numbers of capillaries were identified in temporal stroma but not in their epithelial components. Immunohistochemistry revealed strong, conclusive cytoplasmic immunoreactivity for VEGF in the epithelial cells of both adamantinomatous craniopharyngiomas and papillary craniopharyngiomas. In situ hybridization showed that VEGFR-2 mRNA was expressed widely, not only in neoplastic epithelium but also in capillary endothelium. CONCLUSIONS Tumors with greater microvessel density regrow more frequently compared with tumors that have lower microvessel density, suggesting that the extent of angiogenesis is of prognostic value in patients with craniopharyngioma. VEGFR-2 may act as a key modulator of VEGF activity in endothelial cells and nonendothelial cells, indicating that VEGF plays an important role in the behavior of craniopharyngiomas. Cancer 2002;94:738,45. © 2002 American Cancer Society. DOI 10.1002/cncr.10281 [source] Irradiated fibroblast-induced bystander effects on invasive growth of squamous cell carcinoma under cancer,stromal cell interactionCANCER SCIENCE, Issue 12 2008Noriyuki Kamochi The irradiated fibroblast-induced response of non-irradiated neighboring cells is called ,radiation-induced bystander effect', but it is unclear in non-irradiated human squamous cell carcinoma (SCC) cells. The present study shows that irradiated fibroblasts promoted the invasive growth of T3M-1 SCC cells, but not their apoptosis, more greatly than non-irradiated fibroblasts, using collagen gel invasion assay, immunohistochemistry and Western blot. The number of irradiated fibroblasts decreased to about 30% of that of non-irradiated fibroblasts, but irradiated fibroblasts increased the growth marker ki-67 display of SCC cells more greatly than non-irradiated fibroblasts. Irradiated fibroblasts did not affect the apoptosis marker ss-DNA expression of SCC cells. Irradiated fibroblasts enhanced the display of the following growth-, invasion- and motility-related molecules in SCC cells more greatly than non-irradiated fibroblasts: c-Met, Ras, mitogen-activated protein kinase (MAPK) cascade (Raf-1, MEK-1 and ERK-1/2), matrix metalloproteinase-1 and -9, laminin 5 and filamin A. Irradiated fibroblasts, but not non-irradiated ones, formed irradiation-induced foci (IRIF) of the genomic instability marker p53-binding protein 1 (53BP1) and expressed transforming growth factor-,1 (TGF- ,1). Irradiated fibroblasts in turn enabled SCC cells to enhance 53BP1 IRIF formation more extensively than non-irradiated fibroblasts. Finally, effects of irradiated fibroblasts on growth and apoptosis of another HEp-2 SCC cell type were similar to those of T3M-1. These results suggest that irradiated fibroblasts promotes invasion and growth of SCC cells by enhancement of invasive growth-related molecules above through TGF- ,1-mediated bystander mechanism, in which irradiated fibroblast-induced genomic instability of SCC cells may be involved. (Cancer Sci 2008; 99: 2417,2427) [source] | |||||||||||||||||||||||||