Expression of the integrin alpha 4 beta 1 on melanoma cells can inhibit the invasive stage of metastasis formation.
Among a series of adhesion molecules, expression of integrin alpha 4 beta 1 showed a unique inverse correlation with the invasive potential of B16 melanoma cell lines. When an alpha 4 cDNA was introduced into an alpha 4-beta 1+ highly invasive melanoma line, alpha 4 beta 1 heterodimers were expressed on the surface. Matrigel invasion by the alpha 4+ beta 1+ cells was reduced. Pulmonary metastasis was also suppressed when the transfectants were placed subcutaneously, but not when injected intravenously. Expression of alpha 4 beta 1 promoted homotypic intercellular adhesion. The homotypic adhesion was abrogated, and the alpha 4+ beta 1+ (less invasive cell lines) increased matrigel invasion following the anti-alpha 4 MAb treatment. These results suggest that integrin alpha 4 beta 1 could play a role in controlling melanoma cell metastasis at the invasive stage.
Qian
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Laboratory of Experimental Oncology, Department of Pathology, Stanford University School of Medicine, California 94305.
Vaux
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DL
Weissman
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D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000032:analysis; D003094:Collagen; D018076:DNA, Complementary; D004338:Drug Combinations; D005822:Genetic Vectors; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D007797:Laminin; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D004338:Drug Combinations; D039041:Integrin alpha4beta1; D016023:Integrins; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D016029:Receptors, Very Late Antigen; C059485:matrigel; D003094:Collagen