Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 14, 2013; 19(46): 8630-8637
Published online Dec 14, 2013. doi: 10.3748/wjg.v19.i46.8630
Clinicopathological and biological significance of cripto overexpression in human colon cancer
Peng-Cheng Jiang, Ling Zhu, Yu Fan, Hao-Liang Zhao
Peng-Cheng Jiang, Hao-Liang Zhao, Department of General Surgery, Affiliated First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Ling Zhu, Yu Fan, Cancer Institute, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu Province, China
Author contributions: Jiang PC, Zhu L and Fan Y performed the majority of experiments; Zhao HL and Jiang PC designed the study and wrote the manuscript.
Supported by The National Natural Science Fund, No. 81250035; The Jiangsu Province of 333 Engineering talent fund, No. RA2012103, and Zhenjiang City Social Development Fund No. SH2011031 and SH2011034
Correspondence to: Hao-Liang Zhao, Professor, Department of General Surgery, Affiliated First Hospital of Shanxi Medical University, The liberation of South, Taiyuan 030001, Shanxi Province, China. 18952819981@163.com
Telephone: +86-511-88917999 Fax: +86-511-85234387
Received: June 2, 2013
Revised: August 15, 2013
Accepted: September 29, 2013
Published online: December 14, 2013
Processing time: 198 Days and 15.2 Hours
Abstract

AIM: To assess the clinicopathological and biological significance of cripto in human colorectal cancer.

METHODS: Real-time reverse-transcription polymerase chain reaction (PCR) was used to examine cripto mRNA levels in primary colon cancer and normal colon tissues as well as normal and metastatic lymph nodes from colon cancers. Human colon cancer LS-174T cells were transfected with cripto small interfering RNA (siRNA), and mRNA and protein levels were evaluated using real-time PCR and western blot analysis, respectively. The growth of cancer cells was evaluated using the MTT assay and colony formation in soft agar. Invasion was examined using a Transwell assay, and the expressions of matrix metalloproteinase (MMP)-7 and MMP-9 were determined using western blot assay.

RESULTS: Cripto was significantly overexpressed in primary colon cancer and metastatic lymph nodes. Silencing cripto gene expression with cripto siRNA resulted in a significant decrease in colony formation in soft agar in the colon cancer cell line LS-174T. Cripto siRNA treatment decreased the migration and invasion capabilities of the colon cancer cell line LS-174T in vitro. Furthermore, cripto siRNA treatment inhibited the expression of matrix MMP-7 and MMP-9.

CONCLUSION: The results provide evidence that cripto siRNA could be an effective approach for the inhibition of cancer cell invasion and migration and thus has potential for use in devising novel preventive and therapeutic strategies for colon cancer metastasis.

Keywords: Colon cancer; Invasion; Metastasis; Cripto; Small interfering RNA; Matrix metalloproteinases

Core tip: To assess the clinicopathologic and biological significance of cripto as a novel target for colon cancer gene therapy, pathological and in vitro studies were carried out. Cripto was significantly overexpressed in primary colon cancer and metastatic lymph nodes. In vitro studies found that cripto siRNA resulted in a significant reduction in colony formation in soft agar and in the migration and invasion abilities of colon cancer cells. Furthermore, cripto siRNA led to an inhibition of MMP-7 and MMP-9. These results suggest that the cripto gene be useful for devising novel preventive and therapeutic strategies for colon cancer.