Ligand-Mimetic Anti-αIIbβ3 Antibody PAC-1 Inhibits Tyrosine Signaling, Proliferation and Lung Colonization of Melanoma Cells

Erzsébet RÁSÓ, József TÓVÁRI, Andrea LADÁNYI, Norbert VARGA, József TÍMÁR

Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary


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. Pathology & Oncology Research, Vol 11, Nr 4, 218-223, 2005

Key words: ?IIbß3; integrin; ligand-mimetic; melanoma

Received: Oct 21, 2005; accepted: Nov 11, 2005
Correspondence: József TÍMÁR, Department of Tumor Progression, National Institute of Oncology, Ráth Gy. u. 7-9. Budapest H-1122, Hungary; Tel: 36 1 224 8786, Fax: 36 1 224 8706; E-mail:

Click here to get the full-text version in PDF!