Abstract
Zymography confirmed significant up-regulation of MMP9 activity with dramatic increases in 7 of 10 tumor samples (P= 0.011). Immunoblot analysis of matrix-extracted benign ovary revealed low levels of 65 kDa Fbln5. Interestingly, although expressed in ovarian cancer, Fbln5 degradative products of 52.8 and41.3 kDawere increased substantially in 6 of 8 tumors. Likewise, a Fbln3 degradative product (42 kDa) was present in 5 of 8 tumors, but not in benign tissues. Conclusion: These results suggest a unique matrix microenvironment of EOC characterized by increased MMP9 activity with (i) dramatic down-regulation of its major inhibitor, Timp2, (2) down-regulation of Fbln1, -3, -4 and -5 gene expression, and (3) increased degradation of Fbln5 and Fbln3 thereby generating dominant negative fibulins that promote epithelial cell motility and angiogenesis. We suggest that mechanisms to attenuate protease activation and preservation of Fbln5 in the EOC matrix may serve to inhibit ovarian cancer growth, spread, and MMP9 activity.
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
