Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Apoptosis / physiology
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Cell Division / physiology
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Cell Survival / physiology*
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Enzyme-Linked Immunosorbent Assay
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Extracellular Matrix / metabolism
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Humans
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Melanoma / pathology
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Melanoma / physiopathology*
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Mice
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Mice, SCID
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / physiology*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Vitronectin / antagonists & inhibitors
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Receptors, Vitronectin / physiology*
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Skin Neoplasms / pathology
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Skin Neoplasms / physiopathology*
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Tumor Cells, Cultured
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Vitronectin / metabolism
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bcl-2-Associated X Protein
Substances
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Antibodies, Monoclonal
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BAX protein, human
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Bax protein, mouse
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Vitronectin
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Vitronectin
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bcl-2-Associated X Protein