Carcinogenesis, Vol. 23, No. 2, 237-244,
February 2002
© 2002 Oxford University Press
CANCER BIOLOGY |
Overexpression of 
vß6 integrin in serous epithelial ovarian cancer regulates extracellular matrix degradation via the plasminogen activation cascade
1 Gynaecological Cancer Research Centre, Royal Women's Hospital, Melbourne, Australia,
2 Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia,
3 Perinatal Research Centre, Royal Women's Hospital, Melbourne, Australia,
4 Reproductive Biology Unit, Royal Women's Hospital, Melbourne, Australia,
5 Discipline of Surgical Science, University of Newcastle, NSW, Australia and
6 Laboratory of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Recent evidence suggests that integrins are involved in the multi-step process of tumour metastasis. The biological relevance of 
v integrins and associated ß-subunits in ovarian cancer metastasis was examined by analysing the expression of these cell surface receptors in nine ovarian cancer cell lines and also in the primary human ovarian surface epithelial cell line (HOSE). ß1, ß3 and ß5 subunits were present in all ten ovarian cell lines. ß6 subunit was present at varying levels in eight out of nine cancer cell lines but was absent in the HOSE cell line. Immunohistochemical staining showed that ß6 was present in both non-invasive (borderline) and high-grade ovarian cancer tissues but was absent in benign and normal ovarian tissue. High vß6 integrin expressing ovarian cancer cell lines had high cell surface expression of uPA and uPAR. Ovarian cancer cell lines expressing high to moderate level of vß6 integrin demonstrated ligand-independent enhanced levels of high molecular weight (HMW)-uPA and pro-matrix metalloproteinase 2 and 9 (pro-MMP-2 and pro-MMP-9) expression in the tumour-conditioned medium. High and moderate expression of vß6 integrin correlated with increased plasminogen-dependent degradation of extracellular matrix which could be inhibited by inhibitors of plasmin, uPA and MMPs or by monoclonal antibody against uPA, MMP-9 or vß6 integrin. These results suggest that endogenous de novo expression of vß6 integrin in ovarian cancer cells may contribute to their invasive potential, and that vß6 expression may play a role in ovarian cancer progression and metastasis.
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