Expression and activation of alpha v beta 3 integrins by SDF-1/CXC12 increases the aggressiveness of prostate cancer cells.
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.
Sun
Yan-Xi
YX
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA.
Fang
Ming
M
Wang
Jianhua
J
Cooper
Carlton R
CR
Pienta
Kenneth J
KJ
Taichman
Russell S
RS
D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D039302:Integrin alphaVbeta3