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 αvβ3 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 αvβ 3 receptors by prostate cancer cells to enhance their metastatic behavior by increasing adhesiveness and invasiveness. SDF-1 transiently increased the expression of β3 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 αvβ3 receptors. Activation and increased expression of αvβ 3 within SDF-1-rich organs may participate in metastatic localization.
Original language | English (US) |
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Pages (from-to) | 61-73 |
Number of pages | 13 |
Journal | Prostate |
Volume | 67 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2007 |
Externally published | Yes |
Keywords
- Bone
- Integrin αβ
- Metastasis
- Prostate cancer
- SDF-1
- β phosphorylation
ASJC Scopus subject areas
- Oncology
- Urology