Integrin alpha(v)beta3 promotes M21 melanoma growth in human skin by regulating tumor cell survival.
Growth and dissemination of malignant melanoma has a profound impact on our population, and little is known concerning the mechanisms controlling this disease in humans. Evidence is provided that integrin alpha(v)beta3 plays a critical role in M21 melanoma tumor survival within human skin by a mechanism independent of its known role in angiogenesis. Antagonists of alpha(v)beta3 blocked melanoma growth by inducing tumor apoptosis. Moreover, M21 melanoma cell interactions with denatured collagen, a known ligand for alpha(v)beta3, caused a 5-fold increase in the relative Bcl-2:Bax ratio, an event thought to promote cell survival. Importantly, denatured collagen colocalized with alpha(v)beta3-expressing melanoma cells in human tumor biopsies, suggesting that alpha(v)beta3 interaction with denatured collagen may play a critical role in melanoma tumor survival in vivo.
Petitclerc
E
E
University of Southern California School of Medicine, Department of Biochemistry and Molecular Biology, Norris Cancer Center, Los Angeles 90033, USA.
Strömblad
S
S
von Schalscha
T L
TL
Mitjans
F
F
Piulats
J
J
Montgomery
A M
AM
Cheresh
D A
DA
Brooks
P C
PC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012878:Skin Neoplasms / Q000473:pathology / Q000503:physiopathology*; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000911:Antibodies, Monoclonal; C494826:BAX protein, human; C494827:Bax protein, mouse; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019030:Receptors, Vitronectin; D019096:Vitronectin; D051028:bcl-2-Associated X Protein