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Role of alphaII(b)beta3 integrin in prostate cancer metastasis
1Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48202, USA.
Background:
Integrins participate in cell-cell and cell-matrix interactions. In this study we determined whether alphaII(b)beta3 integrin is involved in metastasis of human prostate adenocarcinoma cells.
Methods:
Prostate adenocarcinoma PC-3 and DU-145 cell lines express alphaII(b)beta3. Northern blotting, 5'-RACE, and immunofluorescent localization confirmed expression of alphaIIb integrin in prostate adenocarcinoma cells. We used orthotopic/ectopic site of implantation and lung colonization assays in SCID mice to determine whether alphaII(b)beta3 participates in metastatasis of tumor cells.
Results:
Immunofluorescent localization of alphaIIb integrin in fibronectin-adherent DU-145 and PC-3 cells is remarkably different. In DU-145 cells the integrin localizes to focal contact sites, whereas it is predominantly intracellular in PC-3 cells. Both tumor cell lines are tumorigenic when implanted subcutaneously or intraprostatically in SCID mice, but only DU-145 cells injected intraprostatically metastasize. Flow cytometry with a mAb directed to alphaII(b)beta3 revealed higher expression of alphaII(b)beta3 in DU-145 tumor cell suspensions isolated from the prostate when compared to DU-145 tumor cells from the subcutis. Function-blocking mAbs to alphaII(b)beta3 inhibit lung colonization of tail vein-injected DU-145 cells.
Conclusions:
Altogether, the data suggest that alphaII(b)beta3 integrin participates in the metastatic progression of prostatic adenocarcinoma.