Beta1 Integrins Mediate Tubule Formation Induced by Supernatants Derived from KSHV-infected Cells

Objective: Angiogenesis is defined as the formation of new blood vessels. In a recently concluded study, we identified Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells derived from primary effusion lymphoma (PEL) to overexpress vascular endothelial growth factor (VEGF) that had the propensity to mediate tubule formation on a Matrigel, an indicator of angiogenesis. The objective of this study was to determine the receptor molecules that mediate the tubule formation induced by the supernatant derived from KSHV-infected PEL cells.

Methods: The identity of receptor(s) that play a role in mediating tubule formation driven by PEL supernatant was determined by the classical in vitro angiogenesis assay conducted on a Matrigel.

Results: RGD peptides, antibodies, and siRNA specific to beta1 integrins significantly lowered the ability of the PEL supernatants to induce tubule formation by endothelial cells. beta1 Integrins mediated tubule formation to comparable levels in endothelial cells that were incubated with supernatants derived from uninduced or TPA-induced PEL cells. Interestingly, the beta1 integrins did not seem to have a major role in cellular attachment.

Conclusion: We report for the first time a critical role for beta1 integrins in angiogenesis supported by the supernatant from KSHV-infected PEL cells.