Role of alphaII(b)beta3 integrin in prostate cancer metastasis.
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.
Trikha
M
M
Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48202, USA.
Raso
E
E
Cai
Y
Y
Fazakas
Z
Z
Paku
S
S
Porter
A T
AT
Timar
J
J
Honn
K V
KV
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D010641:Phenotype; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019039:Platelet Glycoprotein GPIIb-IIIa Complex