Daniel E. Bassi, PhD

Ovarian Tumor Progression

My research interests center in determining the role of a family of nine serine proteases, the proprotein-convertases (PCs) in ovarian tumor progression. Most PCs activate protein precursors after limited proteolysis at the consensus sequence RXR/KR. Many of these precursors are associated with tumor progression, such as growth factors and their receptors, metalloproteinases and adhesion molecules, pointing to a PCs role in regulating tumor progression. For instance, increased expression of these PCs has been correlated with increase histopathological grade and advanced metastatic behavior.

We have determined that increased furin, the prototype of the family, predicts poor survival in ovarian cancer, regardless the specific type of tumor. Moreover, specific blockage of its activity by protein inhibitors and siRNA technology resulted in decreased proliferation and signaling through the insulin-like receptor pathway. Interestingly, a closely related PC, PACE4, also associated with tumor progression in skin and other malignancies, showed an opposite effect in ovarian cancer; more benign and less malignant tumors expressed higher levels of this extracellular protease. In this context, therapies aimed at decreasing ovarian tumor burden should address these differences to exploit this antagonistic effect exerted by these two proteases.