Ligand-mimetic anti-aIIbβ3 antibody PAC-1 inhibits tyrosine signaling, proliferation and lung colonization of melanoma cells

Content Provider	Semantic Scholar
Author	Rásó, Erzsébet Tóvári, József Ladányi, Andrea Varga, Norbert Tímár, József
Copyright Year	2008
Abstract	Abstractβ3 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.
Starting Page	218
Ending Page	223
Page Count	6
File Format	PDF HTM / HTML
DOI	10.1007/BF02893854
Alternate Webpage(s)	http://por.hu/2005/11/4/0218/0218a.pdf
Alternate Webpage(s)	https://doi.org/10.1007/BF02893854
Volume Number	11
Journal	Pathology & Oncology Research
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article