The role of the vitronectin receptor (αvβ 3-integrin) as a tumor promoter seems well established, and, consequently, therapies that block this integrin are currently in clinical testing. We undertook the current study to determine whether αvβ3-integrin is an appropriate target in ovarian cancer treatment. Expression of β3-integrin in SKOV3ip1 ovarian cancer cells led to the overexpression of αvβ 3-integrin on the cell surface and increased adhesion. However, αvβ3-integrinoverexpressing cells showed impaired invasion, protease expression, and colony formation. These results were recapitulated in xenograft studies: αvβ3- integrin-expressing cells showed increased adhesion to mouse peritoneum, but the overall number of metastatic nodules (105 versus 68 tumors) and tumor weight were significantly lower than those in the parental SKOV3ip1 cells. The αvβ3-integrin-overexpressing cells had a decreased proliferation rate mediated by inhibition of cyclin B1 and induction of phospho-Cdc2 and p53 expression, consistent with a G2M cell cycle arrest. Confirming the above results, inhibition of β3-integrin in cultured or primary OvCa cells decreased adhesion but increased invasion and proliferation. Patients with tumors expressing high β3-integrin had significantly better disease-free and overall survival (52 months versus 27 months, P < 0.05). This study shows that αvβ 3-integrin expression on tumor cells actually slows tumor progression and acts as a tumor suppressor. Therefore, the vitronectin receptor might not be an appropriate therapeutic target in ovarian cancer.
ASJC Scopus subject areas
- Pathology and Forensic Medicine