Authors

Marco Trerotola, Prostate Cancer Discovery and Development Program, Thomas Jefferson University; Department of Cancer Biology, Sidney Kimmel Cancer Center; Ce. S.I. - University of Chieti-Pescara
Kirat K Ganguly, Department of Cancer Biology, Prostate Cancer Discovery and Development Program, Thomas Jefferson UniversityFollow
Ladan Fazli, The Vancouver Prostate Centre, University of British Columbia
Carmine Fedele, Department of Cancer Biology, Prostate Cancer Discovery and Development Program, Thomas Jefferson UniversityFollow
Huimin Lu, Prostate Cancer Discovery and Development Program, Thomas Jefferson University; Department of Cancer Biology, Sidney Kimmel Cancer CenterFollow
Anindita Dutta, Prostate Cancer Discovery and Development Program, Thomas Jefferson University; Department of Cancer Biology, Sidney Kimmel Cancer Center
Qin Liu, Prostate Cancer Discovery and Development Program, Thomas Jefferson University; Tumor Microenvironment and Metastasis Program, The Wistar Institute Cancer CenterFollow
Tiziana De Angelis, Prostate Cancer Discovery and Development Program, Thomas Jefferson University; Department of Cancer Biology, Sidney Kimmel Cancer Center
Luke W Riddell, Prostate Cancer Discovery and Development Program, Thomas Jefferson University; Department of Cancer Biology, Sidney Kimmel Cancer Center
Natalia A Riobo, Department of Biochemistry, Thomas Jefferson University
Martin E Gleave, The Vancouver Prostate Centre, University of British Columbia
Amina Zoubeidi, The Vancouver Prostate Centre, University of British Columbia
Richard Pestell, Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Dario C Altieri, Prostate Cancer Discovery and Development Program, Thomas Jefferson University; Tumor Microenvironment and Metastasis Program, The Wistar Institute Cancer CenterFollow
Lucia R Languino, Department of Cancer Biology, Prostate Cancer Discovery and Development Program, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

6-10-2015

Comments

This article has been peer reviewed. It was published in: Oncotarget.

Volume 6, Issue 16, 2015, Pages 14318-14328.

The published version is available at http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=3960&path[]=8612

Copyright © 2015 The Authors

Abstract

In this study, we show that the transmembrane glycoprotein Trop-2 is up-regulated in human prostate cancer (PCa) with extracapsular extension (stages pT3/pT4) as compared to organ-confined (stage pT2) PCa. Consistent with this evidence, Trop-2 expression is found to be increased in metastatic prostate tumors of Transgenic Adenocarcinoma of Mouse Prostate mice and to strongly correlate with α5β1 integrin levels. Using PCa cells, we show that Trop-2 specifically associates with the α5 integrin subunit, as binding to α3 is not observed, and that Trop-2 displaces focal adhesion kinase from focal contacts. In support of the role of Trop-2 as a promoter of PCa metastatic phenotype, we observe high expression of this molecule in exosomes purified from Trop-2-positive PCa cells. These vesicles are then found to promote migration of Trop-2-negative PCa cells on fibronectin, an α5β1 integrin/focal adhesion kinase substrate, thus suggesting that the biological function of Trop-2 may be propagated to recipient cells. In summary, our findings show that Trop-2 promotes an α5β1 integrin-dependent pro-metastatic signaling pathway in PCa cells and that the altered expression of Trop-2 may be utilized for early identification of capsule-invading PCa.

PubMed ID

26015409

Included in

Urology Commons

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