SPOCK1 promotes tumor growth and metastasis in human prostate cancer.
SPOCK1 promotes tumor growth and metastasis in human prostate cancer.
复制标题
DOI：
10.2147/dddt.s91321
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Chen Q;Yao YT;Xu H;Chen YB;Gu M;Cai ZK;Wang Z
前列腺癌是诊断最多的非皮肤癌，是美国男性癌症相关死亡的第二大原因。转移是前列腺癌死亡的主要原因。转移性前列腺癌患者的存活率仅为28%，而局限性前列腺癌患者的存活率接近100%。导致前列腺癌发生的分子机制尚不清楚，本研究探讨了SPARC/Osteonectin、Cwcv和Kazal样域蛋白多糖1(SPOCK1)在前列腺癌进展中的作用。最初，我们发现SPOCK1在前列腺癌组织中的表达明显高于非癌组织。特别是，SPOCK1在转移癌组织中的表达也明显高于非转移癌组织。PC3细胞中SPOCK1的表达被特异性短发夹状RNA抑制，而RWPE-1细胞中SPOCK1的过表达促进了细胞活力、体外集落形成和体内肿瘤生长。此外，PC3细胞中SPOCK1的表达下调与细胞周期停滞于G0/G1期有关，而SPOCK1在RWPE-1细胞中过表达则导致细胞周期停滞于S期。PC3细胞中SPOCK1基因敲除甚至增加了细胞的凋亡率。在前列腺癌的小鼠模型中，SPOCK1的调节也被观察到影响癌细胞的增殖和凋亡过程。此外，在体外，SPOCK1基因敲除减少，而SPOCK1过表达增加细胞的迁移和侵袭能力。注射SPOCK1缺失的PC3细胞可显著减少小鼠肺内的转移结节。这些发现表明，SPOCK1是前列腺癌肿瘤生长和转移的关键介质。
Prostate cancer is the most diagnosed noncutaneous cancer and ranks as the second leading cause of cancer-related deaths in American males. Metastasis is the primary cause of prostate cancer mortality. Survival rate is only 28% for metastatic patients, but is nearly 100% for patients with localized prostate cancers. Molecular mechanisms that underlie this malignancy remain obscure, and this study investigated the role of SPARC/osteonectin, cwcv, and kazal-like domain proteoglycan 1 (SPOCK1) in prostate cancer progression. Initially, we found that SPOCK1 expression was significantly higher in prostate cancer tissues relative to noncancerous tissues. In particular, SPOCK1 expression was also markedly high in metastatic tissues compared with nonmetastatic cancerous tissues. SPOCK1 expression knockdown by specific short hairpin RNA in PC3 cells was significantly inhibited, whereas SPOCK1 overexpression in RWPE-1 cells promoted cell viability, colony formation in vitro, and tumor growth in vivo. Moreover, the SPOCK1 knockdown in PC3 cells was associated with cell cycle arrest in G0/G1 phase, while the SPOCK1 overexpression in RWPE-1 cells induced cell cycle arrest in S phase. The SPOCK1 knockdown in PC3 cells even increased cell apoptosis. SPOCK1 modulation was also observed to affect cancerous cell proliferation and apoptotic processes in the mouse model of prostate cancer. Additionally, the SPOCK1 knockdown decreased, whereas the SPOCK1 overexpression increased cell migration and invasion abilities in vitro. Injection of SPOCK1-depleted PC3 cells significantly decreased metastatic nodules in mouse lungs. These findings suggest that SPOCK1 is a critical mediator of tumor growth and metastasis in prostate cancer.