Involvement of tumor cell integrin alpha v beta 3 in hematogenous metastasis of human melanoma cells.

Autor: Felding-Habermann B; Department of Molecular and Experimental Medicine, Scripps Research Institute, Mail MEM 175, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. brunie@scripps.edu, Fransvea E, O'Toole TE, Manzuk L, Faha B, Hensler M
Jazyk: angličtina
Zdroj: Clinical & experimental metastasis [Clin Exp Metastasis] 2002; Vol. 19 (5), pp. 427-36.
DOI: 10.1023/a:1016377114119
Abstrakt: Early metastasis is the primary cause of death in melanoma patients. The adhesion receptor integrin alpha v beta 3 contributes to tumor cell functions that are potentially involved in melanoma growth and metastasis. We tested whether integrin alpha v beta 3 supports metastasis of human melanoma cells when injected into the bloodstream of immune deficient mice. Comparing variants of the same melanoma cell type that expressed either alpha v beta 3, alpha IIb beta 3 or no beta 3 integrin, we found that only alpha v beta 3 strongly supported metastasis. Inhibition of tumor cell alpha v beta 3 function reduced melanoma metastasis significantly and prolonged animal survival. To understand mechanisms that allow alpha v beta 3, but not alpha IIb beta 3 to support melanoma metastasis, we analyzed proteolytic and migratory activities of the melanoma cell variants. Melanoma cells expressing alpha v beta 3, but not those expressing alpha IIb beta 3 or no beta 3 integrin, produced the active form of metalloproteinase MMP-2 and expressed elevated mRNA levels of MT1-MMP and TIMP-2. This indicates an association between alpha v beta 3 expression and protease processing. Furthermore, alpha v beta 3 expression was required for efficient melanoma cell migration toward the matrix proteins fibronectin and vitronectin. The results suggest that expression of integrin alpha v beta 3 promotes the metastatic phenotype in human melanoma by supporting specific adhesive, invasive and migratory properties of the tumor cells and that the related integrin alpha IIb beta 3 cannot substitute for alpha v beta 3 in this respect.
Databáze: MEDLINE
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