Kudo Satoshi, Saito Hajime, Motoyama Satoru, Sasaki Tomohiko, Imai Kazuhiro, Konno Hayato, Takashima Shinogu, Atari Maiko, Sato Yusuke, Minamiya Yoshihiro
Department of Surgery, Division of Thoracic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita City, 010-8543, Japan.
Tumour Biol. 2015 Sep;36(9):7035-43. doi: 10.1007/s13277-015-3414-2. Epub 2015 Apr 13.
Epithelial-to-mesenchymal transition (EMT) is thought to play a key role in cancer cell invasion and metastasis. We previously demonstrated that cancer cell migration is inhibited by C-reactive protein (CRP), which is widely used as a biomarker of inflammation, though its functions are not fully understood. In the present study, we evaluated the effect of CRP on cancer cell migration and expression of mesenchymal and epithelial markers of EMT and of related transcription factors. MCA-38 murine colon adenocarcinoma cells were subcutaneously inoculated into the backs of C57BL/6 mice, which also received 1 μg of recombinant mouse CRP or vehicle (phosphate-buffered saline) subcutaneously every 3 days for 4 weeks. Thereafter, the mice were sacrificed for evaluation using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. There was no statistical difference in tumor size between the control and CRP groups, but CRP dose-dependently inhibited MCA-38 cell migration. PCR analysis confirmed that CRP suppresses expression of N-cadherin (p < 0.01), a mesenchymal marker of EMT, and ZEB-1, an EMT-related transcription factor (p < 0.01). These findings suggest that CRP inhibits EMT in a MCA-38 tumor-bearing mouse model. CRP may thus be a potentially useful tool for preventing cancer progression through suppression of EMT.
上皮-间质转化（EMT）被认为在癌细胞侵袭和转移中起关键作用。我们之前证明，C反应蛋白（CRP）可抑制癌细胞迁移，CRP作为炎症生物标志物被广泛使用，但其功能尚未完全明确。在本研究中，我们评估了CRP对癌细胞迁移以及EMT的间质和上皮标志物及相关转录因子表达的影响。将MCA-38小鼠结肠腺癌细胞皮下接种到C57BL/6小鼠背部，每3天皮下给予1μg重组小鼠CRP或赋形剂（磷酸盐缓冲盐水），持续4周。之后，处死小鼠，采用定量实时聚合酶链反应（PCR）和免疫组织化学进行评估。对照组和CRP组之间肿瘤大小无统计学差异，但CRP剂量依赖性抑制MCA-38细胞迁移。PCR分析证实，CRP可抑制EMT的间质标志物N-钙黏蛋白（p<0.01）和EMT相关转录因子ZEB-1的表达（p<0.01）。这些发现表明，在携带MCA-38肿瘤的小鼠模型中，CRP可抑制EMT。因此，CRP可能是通过抑制EMT预防癌症进展的潜在有用工具。
