Integrin α5 triggers the metastatic potential in renal cell carcinoma

The therapy of advanced renal cell carcinoma (RCC) is still a major challenge. To intervene therapeutically a deeper comprehension of the particular steps of metastasis is necessary. In this context membrane bound receptors like integrins play a decisive role. We analyzed the integrin alpha 5 expression in 141 clear cell RCC patients by Western blot. Patients with RCC expressed a significant higher level of integrin alpha 5 in tumor than in normal tissue. The integrin alpha 5 expression correlated with tumor grade, the development of distant metastases within five years after tumor nephrectomy and reduced survival. The RCC cell lines Caki-1 and CCF-RC1, which highly express integrin alpha 5, were treated with fibronectin in combination with or without an inhibiting anti-integrin alpha 5 antibody. Afterwards the migration, adhesion, viability and prominent signaling molecules were analyzed. Both cell lines showed a significant reduced migration potential as well as a decreased adhesion potential to fibronectin after treatment with an integrin alpha 5 blocking antibody. A contribution of the AKT and ERK1/2 signaling pathways could be demonstrated. The results indicate integrin alpha 5 as a potent marker to discriminate patients' tumor prognosis. Consequently the integrin subunit alpha 5 can be considered as a target for individual therapy of advanced RCC.