Integrin expression in malignant melanoma and their role in cell attachment and migration on extracellular matrix proteins.
The interaction between melanoma cells and extracellular matrix (ECM) components may be important for invasion and metastasis. The integrins belong to a family of protein heterodimers composed of alpha and beta subunits and the beta 1-integrins are especially important as ECM receptors. We investigated the expression of beta 1-integrins on four human melanoma cell lines (two primary, one from the radial growth phase (RGP) and another from the vertical growth phase (VGP), and two metastatic) and examined their attachment and migration on laminin (LN), type IV collagen (CN) and fibronectin (FN). Among LN and/or CN integrin receptors, only alpha 2 beta 1 (VLA2) was expressed at significantly higher levels in the VGP and metastatic cell lines in comparison to the RGP cell line. In addition, enhanced attachment and migration on LN and CN were significantly inhibited by anti-VLA2 monoclonal antibody (mAb). As to FN receptors, alpha 4 beta 1 and alpha 5 beta 1 expression was heterogeneous among the cell lines, however, it was directly related to enhanced attachment and migration on FN, which also could be inhibited by anti-VLA4 and anti-VLA5 mAbs. Our findings provide evidence for a role in beta 1-integrins, in particular alpha 2 beta 1, in melanoma progression and metastasis.
Etoh
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Pathology Department, Harvard Medical School, Massachusetts General Hospital, Boston.
Byers
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HR
Mihm
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MC
D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003094:Collagen / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D007797:Laminin / Q000502:physiology; D008546:Melanoma, Experimental / Q000503:physiopathology*; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D003094:Collagen