Department of Basic and Clinic Oncology, Faculty of Medicine, University of Chile, Santiago 8389100, Chile.
Asian J Androl. 2019 Nov-Dec;21(6):557-564. doi: 10.4103/aja.aja_23_19.
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.
富含半胱氨酸的酸性分泌蛋白(SPARC)是一种在骨组织中高度表达的基质细胞蛋白,作为趋化因子促进前列腺癌(PCa)细胞向骨髓转移。然而,SPARC 在肿瘤早期进展过程中的作用仍不清楚。在这项研究中,我们发现 SPARC 在具有更高 Gleason 评分的 PCa 组织中高表达。通过分别在 PC3 和 LNCaP 细胞中稳定敲低和过表达 SPARC,我们证明内源性 SPARC 诱导上皮-间充质转化(EMT),降低 E-钙黏蛋白和细胞角蛋白 18,增加 N-钙黏蛋白和波形蛋白。此外,SPARC 诱导 EMT 调节转录因子 Snail 家族转录抑制因子 1(Snail)、Snail 家族转录抑制因子 2(Slug)和锌指 E-盒结合同源框 1(Zeb1)的表达。此外,SPARC 在 PC3 细胞中的敲低减少了体外迁移和侵袭,而不改变细胞增殖。我们的结果表明,SPARC 可能通过改变癌细胞的细胞表型促进肿瘤进展。