Integrin alpha 6 expression in human prostate carcinoma cells is associated with a migratory and invasive phenotype in vitro and in vivo.
Cell adhesion and migration are important features in tumor invasion, being mediated in part by integrins (extracellular matrix receptors). Integrins are significantly decreased in human prostate cancer. An exception is alpha 6 integrin (laminin receptor) which persists during prostate tumor progression. We have selected high (DU-H) and low (DU-L) expressors of alpha 6 integrin from a human prostate tumor cell line, DU145, to assess experimentally the importance of alpha 6 integrin in tumor invasion. DU-H cells exhibited a four-fold increased expression of alpha 6 integrin on the surface compared to DU-L cells. Both cell types contained similar amounts of alpha 3 and alpha 5 integrin. The DU-H cells contained alpha 6 subunits complexed with both the beta 1 and beta 4 subunits whereas DU-L cells contained alpha 6 complexed only with beta 4. DU-H cells were three times more mobile on laminin as compared to DU-L, but adhered similarly on laminin. Adhesion and migration were inhibited with anti-alpha 6 antibody. Each subline was injected intraperitoneally into SCID mice to test its invasive potential. Results showed greater invasion of DU-H compared to DU-L cells, with increased expression of alpha 6 integrin on the tumor at the areas of invasion. These data suggest that alpha 6 integrin expression is advantageous for prostate tumor cell invasion.
Rabinovitz
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Department of Radiation Oncology, University of Arizona Cancer Center, Tucson 85724, USA.
Nagle
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RB
Cress
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D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001485:Basement Membrane / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D006801:Humans; D039503:Integrin alpha6; D007797:Laminin / Q000502:physiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D039503:Integrin alpha6; D007797:Laminin