Specific alpha v integrin receptors modulate K1735 murine melanoma cell behavior.
Expression of beta 3 integrins is increased in invasive melanoma. In this study we show that K1735 cell proliferation is enhanced by the expression of either beta 3 or a constitutively active Src. We investigated possible modulators of FN matrix assembly and found that matrix metalloproteinase 2 (MMP2) was activated by alpha v beta 3. alpha v beta 3 integrin was localized to focal contacts whereas alpha v beta 5 was peripherally distributed. MMP2 was also activated by expression of CASrc. MMP2 activation inversely correlated with FN matrix assembly, in that it dramatically reduced the organization of a FN matrix. K1735 cell migration on VN and invasion through a reconstituted basement membrane were decreased in the presence of anti-MMP2 antibodies. These results demonstrate that the expression of the alpha v beta 3 complex modulates melanoma cell behavior including activation of Src, organization of the cytoskeleton, assembly of the extracellular matrix, cell motility, and activation of MMP2.
Yang
Yongjian
Y
Department of Stomatology, University of California at San Francisco, San Francisco, CA, USA.
Dang
Dongmin
D
Atakilit
Amha
A
Schmidt
Brian
B
Regezi
Joseph
J
Li
Xiaowu
X
Eisele
David
D
Ellis
Duncan
D
Ramos
Daniel M
DM
D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D002465:Cell Movement; D004396:Coloring Agents / Q000494:pharmacology; D006224:Cricetinae; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D039564:Integrin alphaV / Q000378:metabolism / Q000502:physiology*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D010641:Phenotype; D012190:Retroviridae / Q000235:genetics; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D004396:Coloring Agents; D005353:Fibronectins; D039564:Integrin alphaV; D039302:Integrin alphaVbeta3; D013778:Tetrazolium Salts; D013844:Thiazoles; D019096:Vitronectin; D019061:src-Family Kinases; D020778:Matrix Metalloproteinase 2; C022616:thiazolyl blue; D001973:Bromodeoxyuridine