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Abstract

Volume 21, Issue 6 (November 2019) 21, 557–564; 10.4103/aja.aja_23_19

Secreted protein acidic and rich in cysteine (SPARC) induces epithelial-mesenchymal transition, enhancing migration and invasion, and is associated with high Gleason score in prostate cancer

Fernanda López-Moncada, María José Torres, Enrique A Castellón, Héctor R Contreras

Department of Basic and Clinic Oncology, Faculty of Medicine, University of Chile, Santiago 8389100, Chile

Correspondence: Dr. HR Contreras (hcontrer@med.uchile.cl)

23-Apr-2019

Abstract

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein highly expressed in bone tissue that acts as a chemoattractant factor promoting the arrival of prostate cancer (PCa) cells to the bone marrow. However, the contribution of SPARC during the early stages of tumor progression remains unclear. In this study, we show that SPARC is highly expressed in PCa tissues with a higher Gleason score. Through stable knockdown and overexpression of SPARC in PC3 and LNCaP cells, respectively, here we demonstrate that endogenous SPARC induces the epithelial-mesenchymal transition (EMT), decreasing E-cadherin and cytokeratin 18 and increasing N-cadherin and vimentin. Moreover, SPARC induces the expression of EMT regulatory transcription factors Snail family transcriptional repressor 1 (Snail), Snail family transcriptional repressor 2 (Slug), and zinc finger E-box binding homeobox 1 (Zeb1). In addition, SPARC knockdown in PC3 cells decreases migration and invasion in vitro, without modifying cell proliferation. Our results indicate that SPARC might facilitate tumor progression by modifying the cellular phenotype in cancer cells.

Keywords: epithelial-mesenchymal transition; invasion; migration; prostate cancer; secreted protein acidic and rich in cysteine (SPARC)

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