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Role of αIIbβ3 integrin in prostate cancer metastasis
Author(s) -
Trikha Mohit,
Raso Erzsebet,
Cai Yinlong,
Fazakas Zsolt,
Paku Sandor,
Porter Arthur T.,
Timar Jozsef,
Honn Kenneth V.
Publication year - 1998
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19980515)35:3<185::aid-pros4>3.0.co;2-g
Subject(s) - metastasis , integrin , pathology , adenocarcinoma , prostate cancer , prostate , cancer research , fibronectin , biology , flow cytometry , cell , medicine , cancer , microbiology and biotechnology , genetics
BACKGROUND Integrins participate in cell‐cell and cell‐matrix interactions. In this study we determined whether αIIbβ3 integrin is involved in metastasis of human prostate adenocarcinoma cells. METHODS Prostate adenocarcinoma PC‐3 and DU‐145 cell lines express αIIbβ3. Northern blotting, 5′‐RACE, and immunofluorescent localization confirmed expression of αIIb integrin in prostate adenocarcinoma cells. We used orthotopic/ectopic site of implantation and lung colonization assays in SCID mice to determine whether αIIbβ3 participates in metastatasis of tumor cells. RESULTS Immunofluorescent localization of αIIb 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 αIIbβ3 revealed higher expression of αIIbβ3 in DU‐145 tumor cell suspensions isolated from the prostate when compared to DU‐145 tumor cells from the subcutis. Function‐blocking mAbs to αIIbβ3 inhibit lung colonization of tail vein‐injected DU‐145 cells. CONCLUSIONS Altogether, the data suggest that αIIbβ3 integrin participates in the metastatic progression of prostatic adenocarcinoma. Prostate 35:185–192, 1998. © 1998 Wiley‐Liss, Inc.