Expression and activation of alpha v beta 3 integrins by SDF-1/CXC12 increases the aggressiveness of prostate cancer cells.
Prostate
; 67(1): 61-73, 2007 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-17034033
ABSTRACT
BACKGROUND:
Stromal cell-derived factor-1 (SDF-1 or CXCL12) and CXCR4 are key elements in the metastasis of prostate cancer cells to bone--but the mechanisms as to how it localizes to the marrow remains unclear.METHODS:
Prostate cancer cell lines were stimulated with SDF-1 and evaluated for alterations in the expression of adhesion molecules using microarrays, FACs, and Western blotting to identify alpha(v)beta(3) receptors. Cell-cell adhesion and invasion assays were used to verify that activation of the receptor is responsive to SDF-1.RESULTS:
We demonstrate that SDF-1 transiently regulates the number and affinity of alpha(v)beta(3) receptors by prostate cancer cells to enhance their metastatic behavior by increasing adhesiveness and invasiveness. SDF-1 transiently increased the expression of beta(3) receptor subunit and increased its phosphorylation in metastatic but not nonmetastatic cells.CONCLUSIONS:
The transition from a locally invasive phenotype to a metastatic phenotype may be primed by the elevated expression of alpha(v)beta(3) receptors. Activation and increased expression of alpha(v)beta(3) within SDF-1-rich organs may participate in metastatic localization.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Regulação Neoplásica da Expressão Gênica
/
Quimiocinas CXC
/
Integrina alfaVbeta3
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos