Integrin expression in human melanoma cells with differing invasive and metastatic properties.
During the process of tumor cell invasion and metastasis, tumor cells are known to interact with extracellular matrix proteins, endothelial cells, platelets and other organ-specific structures. Integrins are cell surface molecules which mediate cell-matrix and cell-cell interactions and are likely to be important for tumor cell survival and dissemination. The purpose of this study was to characterize the integrin and proteolytic enzyme repertoire from low (A375P), medium (A375M) and high metastatic (A375SM) human melanoma cell lines. These cell lines are also invasive through human amniotic membranes in vitro and their invasiveness parallels the reported metastatic phenotype. The types and levels of expression of the various integrin receptors were analysed by quantitative immunoprecipitation using a panel of monoclonal antibodies directed to known integrin subunits. In addition, cDNA probes to the integrin subunits were used in quantitative northern blot analysis. These data show that the integrin alpha v beta 3 increases 50- to 100-fold as these cells progress to a more metastatic phenotype. alpha 4 beta 1 levels also appeared to increase several fold, while other beta 1 integrins did not differ in their expression levels. The increased alpha v beta 3 expression in the more metastatic cells resulted in an increased adhesion to vitronectin and fibrinogen substrates in cell attachment assays. However, alpha v- and beta 3-specific antibodies did not inhibit A375 cell invasion through the amnion. Each cell line was found to release similar quantities of a 72-kDa gelatinase/type IV collagenase and tissue type plasminogen activator. These results suggest that during the progression of these tumor cells from a low to high metastatic phenotype, marked changes in integrin expression occurred which may facilitate interactions with platelets, endothelial cells and specific extracellular matrix proteins to promote metastasis.
Gehlsen
K R
KR
La Jolla Institute for Experimental Medicine, CA.
Davis
G E
GE
Sriramarao
P
P
D002448:Cell Adhesion; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D003012:Microbial Collagenase / Q000302:isolation & purification; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009366:Neoplasm Seeding; D010641:Phenotype; D011233:Precipitin Tests; D014407:Tumor Cells, Cultured
D003470:Culture Media; D016023:Integrins; D003012:Microbial Collagenase