Role of αIIbβ3 integrin in prostate cancer metastasis

Mohit Trikha, E. Rásó, Yinlong Cai, Zsolt Fazakas, S. Paku, Arthur T. Porter, J. Tímár, Kenneth V. Honn

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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 aIIbβ3 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.

Original languageEnglish
Pages (from-to)185-192
Number of pages8
JournalProstate
Volume35
Issue number3
DOIs
Publication statusPublished - May 15 1998

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Integrins
Prostatic Neoplasms
Neoplasm Metastasis
Prostate
Adenocarcinoma
SCID Mice
Neoplasms
Lung
Focal Adhesions
Tumor Cell Line
Fibronectins
Cell Communication
Northern Blotting
Tail
Veins
Suspensions
Flow Cytometry
Cell Line

Keywords

  • DU-145
  • Ectopic
  • Immunofluorescence
  • Orthotopic
  • PC-3

ASJC Scopus subject areas

  • Urology

Cite this

Role of αIIbβ3 integrin in prostate cancer metastasis. / Trikha, Mohit; Rásó, E.; Cai, Yinlong; Fazakas, Zsolt; Paku, S.; Porter, Arthur T.; Tímár, J.; Honn, Kenneth V.

In: Prostate, Vol. 35, No. 3, 15.05.1998, p. 185-192.

Research output: Contribution to journalArticle

Trikha, Mohit ; Rásó, E. ; Cai, Yinlong ; Fazakas, Zsolt ; Paku, S. ; Porter, Arthur T. ; Tímár, J. ; Honn, Kenneth V. / Role of αIIbβ3 integrin in prostate cancer metastasis. In: Prostate. 1998 ; Vol. 35, No. 3. pp. 185-192.
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AB - 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 aIIbβ3 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.

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