Invasive Properties (invasive + property)

Distribution by Scientific Domains

Selected Abstracts

CD44 variant isoform v10 is expressed on tumor-infiltrating lymphocytes and mediates hyaluronan-independent heterotypic cell,cell adhesion to melanoma cells

T. K. Weimann
Abstract: CD44 is a family of cell-surface receptors on human lymphocytes that act as co-stimulatory molecules leading to the induction of effector functions in T cells. We have analyzed primary cutaneous malignant melanomas with clinical and histologic signs of tumor regression using immunohistochemistry and observed the predominant expression of the CD44 variant isoform v10 on CD3 CD4/CD8 co-expressing tumor-infiltrating lymphocytes (TIL). We further analyzed the role of CD44v10 in adhesion of lymphocytes to human melanoma cells. In contrast to CD44, lymphatic cells, CD44v10+ lymphatic cells strongly bound to cultured human melanoma cells and to frozen tissue samples of melanomas. Antibody blocking studies revealed a hyaluronan-, integrin-, and selectin-independent pathway of adhesion. Furthermore, CD44v10+ lymphatic cells exhibited significantly higher invasiveness in three-dimensional collagen matrices as compared with CD44H+ and CD44-negative lymphocytes. These results indicate that expression of CD44v10 on TIL may mediate adhesion to melanoma cells and result in gain of novel invasive properties. [source]

Dominant-negative CREB inhibits heparanase functionality and melanoma cell invasion

Rebecca Aucoin
Abstract Heparanase (HPSE-1) is an endo-,- d -glucuronidase involved in the degradation of cell-surface/extracellular matrix heparan sulfate (HS) in normal and neoplastic tissues. HPSE-1 represents the first example of purification and cloning of a mammalian HS-degradative enzyme. Elevated HPSE-1 levels are known to be associated with metastatic cancers, directly implicating HPSE-1 in metastatic events. The purpose of this study was to determine the role of cAMP response element-binding protein (CREB) in modulating HPSE-1-mediated effects on human melanoma cell invasion. Highly invasive, brain-metastatic melanoma cells (70W) were transfected with the dominant-negative CREB (KCREB) and subsequently analyzed for changes in their HPSE-1 content, functionality, and cell invasive properties. KCREB-transfected cells showed a decrease in HPSE-1 mRNA expression and activity. This correlated with a significantly decreased invasion of these cells through Matrigel‘-coated filters. Furthermore, adenoviral vectors containing the full-length human HPSE-1 cDNA in sense orientation (Ad-S/hep) were constructed to investigate CREB effects on HPSE-1. Restoration of HPSE-1 expression and functionality following Ad-S/hep infection of KCREB-transfected 70W cells recovered melanoma cell invasiveness. These results demonstrate that KCREB inhibits HPSE-1 and suggest that one of the roles CREB plays in the acquisition of melanoma cells metastatic phenotype is affecting HPSE-1 activity. © 2004 Wiley-Liss, Inc. [source]

Identification of immunogenic cell wall-associated proteins of Streptococcus suis serotype 2

Anding Zhang
Abstract Streptococcus suis serotype 2 (SS2) is a porcine and human pathogen with adhesive and invasive properties. The absence of suitable vaccine or virulent marker can be the bottleneck to control SS2 infection. An immunoproteome-based approach was developed to identify candidate antigens of SS2 for vaccine development. Hyperimmune sera, convalescent sera, and control sera were analyzed for reactivity by Western Blot against SS2 cell wall-associated proteins (WAPs) separated by 2-DE. A total of 34 proteins were identified by immunoproteomic analysis, of which 15 were recognized by both hyperimmune sera and convalescent sera, including most WAPs currently characterized as SS2 vaccine candidate antigens: muramidase-released protein (MRP), surface protein SP1 (Sao), and glyceraldehyde-3-phosphate dehydrogenase (GapdH). The novel immunogenic proteins may be developed as alternative antigens for further study of SS2 vaccine and diagnostics. [source]

Epithelial,mesenchymal transition in cancer development and its clinical significance

CANCER SCIENCE, Issue 2 2010
Masaaki Iwatsuki
The epithelial,mesenchymal transition (EMT) plays a critical role in embryonic development. EMT is also involved in cancer progression and metastasis and it is probable that a common molecular mechanism is shared by these processes. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. Furthermore, the acquisition of EMT features has been associated with chemoresistance which could give rise to recurrence and metastasis after standard chemotherapeutic treatment. Thus, EMT could be closely involved in carcinogenesis, invasion, metastasis, recurrence, and chemoresistance. Research into EMT and its role in cancer pathogenesis has progressed rapidly and it is now hypothesized that novel concepts such as cancer stem cells and microRNA could be involved in EMT. However, the involvement of EMT varies greatly among cancer types, and much remains to be learned. In this review, we present recent findings regarding the involvement of EMT in cancer progression and metastasis and provide a perspective from clinical and translational viewpoints. (Cancer Sci 2009) [source]

Roles of pericellular proteolysis by membrane type-1 matrix metalloproteinase in cancer invasion and angiogenesis

CANCER SCIENCE, Issue 7 2003
Motoharu Seiki
Behavior of cancer cells is profoundly affected by their microenvironment, which is often controlled by pericellular proteolysis or the processing of protein components, including extracellular matrices, growth factors, cytokines, receptors, cell adhesion molecules, and so on. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases responsible for the proteolytic events in the extracellular milieu. Among the multiple MMPs expressed in a wide range of tumors, membrane type-1 MMP (MT1-MMP), which is expressed especially in tumor cells with significant invasive properties, is thought to be particularly important for pericellular proteolysis. Recent studies have elucidated in part how MT1-MMP is regulated biologically for the promotion of invasion by tumors or for angiogenesis by endothelial cells. Understanding of the proteolysis by, and the regulation of MT1-MMP, which probably promotes cell invasion, could provide a therapeutic hint as to how to block or delay the progression of cancer. [source]

Low Ki-67 proliferation index is an indicator of poor prognosis in gastric cancer

Hee Eun Lee MD
Abstract Background and Objectives We designed this study to assess the biologic significance of Ki-67 proliferation index (PI) in gastric cancer. Methods Gastric cancer tissue from 245 patients were immunostained for Ki-67. Ki-67 PI was defined as the percentage of tumor cells positive for Ki-67. In addition, we have previously evaluated the expressions of nine epithelial mesenchymal transition (EMT)-related proteins. The relationship between Ki-67 PI and clinicopathologic parameters, patient survival, and EMT data were sought. Results Low Ki-67 PI was correlated with poorly differentiated histology (P,=,0.034), an advanced T stage (P,<,0.001), and lymph node metastasis (P,=,0.011). Also, the low PI group was found to have a significantly worse prognosis than the high PI group (P,=,0.003, log-rank test). Multivariate analysis revealed that Ki-67 PI remained as an independent prognostic factor (hazard ratio (95% CI),=,0.670 (0.450,0.999)). Furthermore, greater expressional changes of EMT-related proteins were found to be significantly associated with low Ki-67 PI (P,=,0.025). Conclusions These findings suggest that Ki-67 PI is an effective tool for predicting survival in gastric cancer. In addition, we found that an invasive property presented as EMT-related protein expressional changes was inversely correlated with a proliferative activity in gastric cancer. J. Surg. Oncol. 2010;102:201,206. © 2010 Wiley-Liss, Inc. [source]

Outcome after radical prostatectomy with a pretreatment prostate biopsy Gleason score of ,8

M. Manoharan
The use of radical prostatectomy to treat patients with high-grade prostate cancer is the subject of much discussion, and the authors from Miami present their considerable experience in this field. They show that patients with a pre-treatment biopsy of Gleason score of ,8 may benefit from radical prostatectomy, assuming a clinical stage of T1,T2, and particularly if their PSA level is <20 ng/mL. Authors from Palermo present data on the long-term outcome of antiandrogen monotherapy in advanced prostate cancer, with the 12-year results of a phase II study. This is a very interesting evaluation, showing that patients with an early objective response have a prolonged progression-free and overall survival. In a large series of superficial bladder tumours, urologists from Tokyo identify a group of patients with tumours of low malignant potential with a high recurrence rate, but a very low invasive property. They suggest that those tumours should be referred to as having a low malignant potential, rather than being called superficial bladder carcinoma. OBJECTIVE To determine the outcome and predictors of recurrence in patients with a pretreatment prostate biopsy Gleason score (GS) of ,,8 and treated with radical prostatectomy (RP). PATIENTS AND METHODS We retrospectively reviewed 1048 consecutive patients who underwent RP by one surgeon (M.S.S.); patients who had a pretreatment biopsy GS of ,,8 were identified. Information was recorded on patient age, initial prostate specific antigen (PSA) level, clinical stage, biopsy GS, pathology GS, extraprostatic extension (EPE), tumour volume, surgical margin status, seminal vesicle invasion (SVI), and lymph node involvement. The results were assessed statistically using the Kaplan-Meier method, univariate log-rank tests and multivariate analysis using Cox's proportional hazards regression. RESULTS In all, 123 patients met the initial selection criteria; 44 were excluded from further analyses (five salvage RP, 23 <,1 year follow-up and 16 adjuvant treatment). Thus 79 patients were included in the uni- and multivariate analyses; 25 (31%) patients had a GS of ,,7 in the RP specimen and 54 (69%) remained at GS ,,8. The mean follow-up was 55 months, the age of the patients 63 years and the mean (sd) initial PSA level 13 (12) ng/mL. The overall biochemical failure rate was 38% (41% if the final GS was , 8 and 32% if it was ,,7). For those with a GS of ,,8 in the RP specimen, 20% (11/54) were organ-confined; two patients (2.5%) in this group developed local recurrence. If the final GS was ,,7, 52% (13/25) were organ-confined. In the univariate analysis, significant risk factors for recurrence were PSA ,,20 ng/mL, EPE, SVI, a positive surgical margin and tumour volume. Cox's proportional regression indicated that a PSA of ,,20 ng/mL (hazard ratio 7.9, 95% confidence interval 2.6,24.2, P < 0.001), the presence of EPE (4.2, 1.6,10.9, P = 0.004) and a positive surgical margin (3.8, 1.5,9.7, P = 0.005) were significant independent predictors in a multivariate analysis. CONCLUSION RP is a reasonable treatment option for patients with a prostate biopsy GS of ,8 and clinical stage T1,2. These patients have a high chance of remaining disease-free if their PSA level is ,,20 ng/mL. Patients with a pretreatment biopsy GS of ,,8 should be counselled about the potential differences between the biopsy and the RP specimen GS. [source]