Integrin beta 3 cDNA transfection into a highly metastatic alpha v beta 3-negative human melanoma cell line inhibits invasion and experimental metastasis.
Even though integrin alpha v beta 3 is thought to play a role in invasive growth of melanomas, some metastatic melanoma cell lines lack alpha v beta 3, and downmodulation of alpha v beta 3, expression can enhance the invasive capacity of certain melanoma cells. To further investigate this apparent dualistic role of alpha v beta 3, we transfected beta 3 cDNA into the highly metastatic, beta 3-negative human melanoma cell line MV3. MV3 cells adhered to fibronectin but not to fibrinogen or a synthetic RGD peptide, while MV3-beta 3 adhered to all three RGD-containing adhesive ligands, and this adhesion was inhibited by LM609 alpha v beta 3 mAb. Expression of alpha v beta 3 did not affect MV3 in vitro proliferation or in vivo tumorigenicity upon subcutaneous inoculation into nude mice. In contrast, it strongly reduced invasion in matrigel and lung colonization in nude mice of MV3 cells. Thus, certain melanoma cell lines have adopted a metastatic strategy in the absence of alpha v beta 3, and in such cells expression of this integrin leads to a less aggressive phenotype.
Danen
E H
EH
Department of Pathology, University Hospital St. Radboud, Nijmegen, The Netherlands.
van Kraats
A A
AA
Cornelissen
I M
IM
Ruiter
D J
DJ
van Muijen
G N
GN
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D018076:DNA, Complementary; D006801:Humans; D039661:Integrin beta3; D008175:Lung Neoplasms / Q000556:secondary; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009368:Neoplasm Transplantation; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018076:DNA, Complementary; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins