Role of αIIbβ3 integrin in prostate cancer metastasis

✍ Scribed by Trikha, Mohit; Raso, Erzsebet; Cai, Yinlong; Fazakas, Zsolt; Paku, Sandor; Porter, Arthur T.; Timar, Jozsef; Honn, Kenneth V.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 497 KB
• Volume: 35
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(19980515)35:3<185::aid-pros4>3.0.co;2-g

✦ Synopsis

BACKGROUND.

Integrins participate in cell-cell and cell-matrix interactions. In this study we determined whether ␣IIb␤3 integrin is involved in metastasis of human prostate adenocarcinoma cells. METHODS. Prostate adenocarcinoma PC-3 and DU-145 cell lines express ␣IIb␤3. Northern blotting, 5Ј-RACE, and immunofluorescent localization confirmed expression of ␣IIb integrin in prostate adenocarcinoma cells. We used orthotopic/ectopic site of implantation and lung colonization assays in SCID mice to determine whether ␣IIb␤3 participates in metastatasis of tumor cells. RESULTS. Immunofluorescent localization of ␣IIb 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 ␣IIb␤3 revealed higher expression of ␣IIb␤3 in DU-145 tumor cell suspensions isolated from the prostate when compared to DU-145 tumor cells from the subcutis. Function-blocking mAbs to ␣IIb␤3 inhibit lung colonization of tail vein-injected DU-145 cells. CONCLUSIONS. Altogether, the data suggest that ␣IIb␤3 integrin participates in the metastatic progression of prostatic adenocarcinoma.