Sang Weilin, Zhu Libo, Ma Jinzhong, Lu Haiming, Wang Cong
The Affiliated First People's Hospital, Shanghai Jiaotong University , Shanghai, China .
Cancer Biother Radiopharm. 2016 Apr;31(3):91-8. doi: 10.1089/cbr.2014.1758. Epub 2016 Apr 4.
Collagen triple helix repeat containing-1 (CTHRC1), a secreted protein, is transiently expressed in the arterial wall in response to injury, indicating that it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration. Recent studies showed that it is aberrantly upregulated in most human solid tumors, yet its role in osteosarcoma remains unclear. In this study, the authors investigated the role of CTHRC1 in human osteosarcoma tumorigenesis. The authors used lentivirus-mediated short hairpin RNA (shRNA) against CTHRC1 to limit its endogenous expression in U2OS and SW1353 cells. Interestingly, they found that depletion of CTHRC1 significantly inhibited cell proliferation and colony formation in U2OS and SW1353 cells. Flow cytometry assay showed that knockdown of CTHRC1 increased the cell percentage of G0/G1 phase, resulting in cell cycle arrest in U2OS cells. Moreover, CTHRC1 silencing induced the cell cycle arrest by a decrease in the cell percentage in G0/G1 phase and increased in G2/M phase in SW1353 cells. In addition, crystal violet staining suggested CTHRC1 silencing inhibited migration of U2OS and SW1353 cells. These results demonstrated that CTHRC1 might play an important role in osteosarcoma progression.
含胶原蛋白三螺旋重复序列-1（CTHRC1）是一种分泌蛋白，在动脉壁受到损伤时会短暂表达，这表明它可能通过限制胶原蛋白基质沉积和促进细胞迁移来参与血管重塑。最近的研究表明，它在大多数人类实体瘤中异常上调，但其在骨肉瘤中的作用仍不清楚。在本研究中，作者调查了CTHRC1在人类骨肉瘤肿瘤发生中的作用。作者使用慢病毒介导的针对CTHRC1的短发夹RNA（shRNA）来限制其在U2OS和SW1353细胞中的内源性表达。有趣的是，他们发现CTHRC1的缺失显著抑制了U2OS和SW1353细胞的增殖和集落形成。流式细胞术检测表明，敲低CTHRC1增加了U2OS细胞中G0/G1期的细胞百分比，导致细胞周期停滞。此外，CTHRC1沉默通过降低SW1353细胞中G0/G1期的细胞百分比并增加G2/M期的细胞百分比来诱导细胞周期停滞。此外，结晶紫染色表明CTHRC1沉默抑制了U2OS和SW1353细胞的迁移。这些结果表明CTHRC1可能在骨肉瘤进展中起重要作用。
