Gastroenterologic Surgery, Kanazawa University, Ishikawa, Japan.
Gastroenterologic Surgery, Kanazawa University, Ishikawa, Japan.
J Surg Res. 2019 May;237:22-29. doi: 10.1016/j.jss.2018.11.014. Epub 2019 Jan 22.
The embryonic stem cell-specific transcription factor, ZFP57, has been shown to play an important role in tumor formation. In this study, we examined if ZFP57 is involved in colorectal cancer metastasis.
First, we used colorectal cancer cell lines to perform in vivo metastatic experiments with nude mice. Next, we carried out immunohistochemical analysis of clinical specimens of colorectal cancers.
In liver metastatic experiments using human colorectal cancer HT29 and HCT116 cells, liver polymetastases occurred at high frequency in ZFP57-overexpressing HT29 and HCT116 cells, whereas both control cells only resulted in oligometastases. Next, we analyzed ZFP57 expression using clinical specimens. Liver metastasis-positive cases were more frequently associated with ZFP57 overexpression than negative cases in primary lesions of colorectal cancer, and the overexpression was particularly remarkable in tumor invasive lesions. Furthermore, ZFP57 overexpression was significantly correlated not only with liver metastasis but also with lymph node metastasis. In addition, the expression level of ZFP57 was significantly correlated with that of the metastasis-related gene NANOG. We also found that ZFP57 overexpression reduced the progression-free survival rate of patients with colorectal cancer.
This study demonstrated that ZFP57 plays an important role in the hematogenous metastasis of colorectal cancer, suggesting that it could be used as a novel treatment target.
胚胎干细胞特异性转录因子 ZFP57 已被证明在肿瘤形成中发挥重要作用。在这项研究中,我们研究了 ZFP57 是否参与结直肠癌转移。
首先,我们使用结直肠癌细胞系在裸鼠体内进行转移实验。接下来,我们对结直肠癌的临床标本进行免疫组织化学分析。
在 ZFP57 过表达 HT29 和 HCT116 细胞的肝转移实验中,高表达 ZFP57 的 HT29 和 HCT116 细胞在肝脏中形成多发性转移灶的频率较高,而对照组细胞仅形成寡转移灶。接下来,我们分析了临床标本中 ZFP57 的表达。在结直肠癌原发灶中,肝转移阳性病例中 ZFP57 过表达的频率高于阴性病例,并且在肿瘤侵袭性病变中过表达更为明显。此外,ZFP57 过表达不仅与肝转移,而且与淋巴结转移显著相关。此外,ZFP57 的表达水平与转移相关基因 NANOG 的表达水平显著相关。我们还发现,ZFP57 过表达降低了结直肠癌患者的无进展生存率。
本研究表明 ZFP57 在结直肠癌的血行转移中起重要作用,提示其可能成为一种新的治疗靶点。