β3 integrin expression is the hallmark of melanoma and may serve as a potential therapeutic target. While αvβ3 integrin expression seems to be constitutive in melanoma, ectopic expression of platelet-αIIbβ3 is dependent on progression. B16a murine melanoma is a suitable model for studies on αIIbβ3 treatment strategies since αvβ3 is not expressed in this cell line. Here we have used a ligand-mimetic anti-αIIbβ3 monoclonal antibody, PAC-1, to test the biological consequences of αIIbβ3 modulation in melanoma cells. We have previously reported that in B16a cells FAK is constitutively active and tyrosine-phosphorylated. Upon PAC-1 binding to the surface αIIbβ3, which is in the active conformation, FAK became dephosphorylated through a process of PKC-dependent phosphatase activation. Furthermore, PAC-1 binding to B16a cells induced a significant decrease in phosphotyrosine-positive melanoma cells within 30 min. Treatment of B16a cells in vitro with PAC-1 significantly inhibited proliferation by decreasing the mitotic index but not affecting apoptotic rate. Incubation of B16a cells with PAC-1 decreased their lung colonization potential, suggesting a profound alteration in their biological behavior under the effect of this antibody. These preclinical data suggest that the ectopic expression of αIIbβ3 in melanoma cells can be exploited as a novel target of antibody therapy of melanoma.
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Cancer Research