ROLE OF ALPHA-IIB-BETA-3 INTEGRIN IN PROSTATE-CANCER METASTASIS

BACKGROUND. Integrins participate in cell-cell and cell-matrix interac tions. In this study we determined whether alpha IIb beta 3 integrin i s involved in metastasis of human prostate adenocarcinoma cells. METHO DS. Prostate adenocarcinoma PC-3 and DU-145 cell lines express alpha I Ib beta 3. Northern blotting, 5'-RACE, and immunofluorescent localizat ion confirmed expression of alpha IIb integrin in prostate adenocarcin oma cells. We used orthotopic/ectoyic site of implantation and lung co lonization assays in SCID mice to determine whether alpha IIb beta 3 p articipates in metastatasis of tumor cells. RESULTS. Immunofluorescent localization of alpha IIb integrin in fibronectin-adherent DU-145 and PC-3 cells is remarkably different. In DU-145 cells the integrin loca lizes to focal contact sites, whereas it is predominantly intracellula r in PC-3 cells. Both tumor cell lines are tumorigenic when implanted subcutaneously or intraprostatically in SCID mice, but only DU-145 cel ls injected intraprostatically metastasize. Flour cytometry with a mAb directed to alpha IIb beta 3 revealed higher expression of alpha IIB beta 3 in DU-145 tumor cell suspensions isolated from the prostate whe n compared to DU-145 tumor cells from the subcutis. Function-blocking mAbs to alpha IIb beta 3 inhibit lung colonization of tail vein-inject ed DU-145 cells. CONCLUSIONS. Altogether, the data suggest that alpha IIb beta 3 integrin participates in the metastatic progression of pros tatic adenocarcinoma. (C) 1998 Wiley-Liss, Inc.