Yasuhiro Shoji1, Hiroyuki Takamura2, Itasu Ninomiya1, Sachio Fushida1, Yuhki Tada3, Takashi Yokota4, Tetsuo Ohta1, Hiroshi Koide5. 1. Gastroenterologic Surgery, Kanazawa University, Ishikawa, Japan. 2. Gastroenterologic Surgery, Kanazawa University, Ishikawa, Japan. Electronic address: takamuh@staff.kanazawa-u.ac.jp. 3. Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan; Technology and Development Team for Mammalian Genome Dynamics, RIKEN BioResource Center, Ibaraki, Japan. 4. Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan. 5. Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan; Laboratory of Molecular and Biochemical Research, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: In liver metastatic experiments using humancolorectal 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. CONCLUSIONS: 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.