Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2016; 22(8): 2503-2511
Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2503
Sphingosine kinase 1 is upregulated with lysophosphatidic acid receptor 2 in human colorectal cancer
Dai Shida, Satoru Inoue, Yuki Yoshida, Atsushi Kodaka, Tsutomu Tsuji, Makoto Tsuiji
Dai Shida, Colorectal Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
Dai Shida, Satoru Inoue, Department of Surgery, Tokyo Metropolitan Bokutoh Hospital, Tokyo 130-8575, Japan
Yuki Yoshida, Atsushi Kodaka, Tsutomu Tsuji, Makoto Tsuiji, Department of Microbiology, Hoshi University School of Pharmaceutical Sciences, Tokyo 142-8501, Japan
Author contributions: Shida D and Tsuiji M participated in the conception and design of the study; Shida D and Inoue S collected the samples; Yoshida Y, Kodaka A, Tsuji T and Tsuiji M performed the assays; Both Shida D and Tsuiji M were responsible for writing the paper and supervising the study.
Supported by Grant 2010 from Tokyo Metropolis, Japan.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Tokyo Metropolitan Bokutoh Hospital (IRB code: 32-Heisei22).
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dai Shida, MD, PhD, Colorectal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. dshida-tky@umin.ac.jp
Telephone: +81-3-35422511 Fax: +81-3-35453567
Received: October 11, 2015
Peer-review started: October 12, 2015
First decision: November 5, 2015
Revised: November 22, 2015
Accepted: December 12, 2015
Article in press: December 14, 2015
Published online: February 28, 2016
Processing time: 137 Days and 10.1 Hours
Abstract

AIM: To examine the expression of SphK1, an oncogenic kinase that produces sphingosine 1-phosphate (S1P), and its correlation with the expression of LPAR2, a major lysophosphatidic acid (LPA) receptor overexpressed in various cancers, in human colorectal cancer.

METHODS: Real-time reverse-transcription polymerase chain reaction was used to measure the mRNA expression of SphK1, LPAR2, and the three major S1P receptors in 27 colorectal cancer samples and corresponding normal tissue samples. We also examined the correlation between the expression of SphK1 and LPAR2.

RESULTS: Colorectal cancer tissue in 22 of 27 patients had higher levels of SphK1 mRNA than in normal tissue. In two-thirds of the samples, SphK1 mRNA expression was more than two-fold higher than in normal tissue. Consistent with previous reports, LPAR2 mRNA expression in 20 of 27 colorectal cancer tissue samples was higher compared to normal tissue samples. Expression profiles of all three major S1P receptors, S1PR1, S1PR2, and S1PR3, varied without any trend, with no significant difference in expression between cancer and normal tissues. A highly significant positive correlation was found between SphK1 and LPAR2 expression [Pearson’s correlation coefficient (r) = 0.784 and P < 0.01]. The mRNA levels of SphK1 and LPAR2 did not correlate with TNM stage.

CONCLUSION: Our findings suggest that S1P and LPA may play important roles in the development of colorectal cancer via the upregulation of SphK1 and LPAR2, both of which could serve as new therapeutic targets in the treatment of colorectal cancer.

Keywords: Sphingosine kinase 1; Lysophosphatidic acid receptor 2; Carcinogenesis; Colorectal cancer; Sphingosine 1-phosphate

Core tip: This is the first study examining the mRNA expression of SphK1, an oncogenic kinase that produces sphingosine 1-phosphate (S1P), at the mRNA level and its correlation with the expression of lysophosphatidic acid receptor 2 (LPAR2), a major lysophosphatidic acid (LPA) receptor overexpressed in various cancers, in human colorectal cancer. Colorectal cancer tissue in 22 of 27 patients had higher levels of SphK1 mRNA than in normal tissue. A highly significant positive correlation was found between SphK1 and LPAR2 expression (r = 0.784 and P < 0.01). Our findings suggest that S1P and LPA may play important roles in the development of colorectal cancer via the upregulation of SphK1 and LPAR2.