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World J Gastrointest Pathophysiol. May 15, 2016; 7(2): 218-222
Published online May 15, 2016. doi: 10.4291/wjgp.v7.i2.218
Clinical impacts of mesothelin expression in gastrointestinal carcinomas
Takahiro Einama, Futoshi Kawamata, Hirofumi Kamachi, Hiroshi Nishihara, Shigenori Homma, Fumihiko Matsuzawa, Tatsuzo Mizukami, Yuji Konishi, Munenori Tahara, Toshiya Kamiyama, Okio Hino, Akinobu Taketomi, Satoru Todo
Takahiro Einama, Futoshi Kawamata, Hirofumi Kamachi, Shigenori Homma, Fumihiko Matsuzawa, Tatsuzo Mizukami, Yuji Konishi, Munenori Tahara, Toshiya Kamiyama, Akinobu Taketomi, Department of General Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
Hiroshi Nishihara, Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
Okio Hino, Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Satoru Todo, Research institute of St. Mary’s Hospital, Kurume 830-8558, Japan
Author contributions: All authors equally contributed to this paper regarding its conception, literature review, editing and approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest.
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: Takahiro Einama, MD, PhD, Department of General Surgery, Hokkaido University Graduate School of Medicine, Kita-Ku, Kita 14, Nishi 7, Sapporo, Hokkaido 060-8638, Japan. titiuehahaue@hotmail.com
Telephone: +81-11-7065927 Fax: +81-11-7177515
Received: September 29, 2015
Peer-review started: October 2, 2015
First decision: November 4, 2015
Revised: December 8, 2015
Accepted: January 27, 2016
Article in press: January 29, 2016
Published online: May 15, 2016
Processing time: 226 Days and 18.5 Hours
Abstract

Mesothelin, C-ERC/mesothelin is a 40-kDa cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura, peritoneum, and pericardium. Moreover, mesothelin has been shown to be overexpressed in several human cancers, including virtually all mesothelioma and pancreatic cancer, approximately 70% of ovarian cancer and extra bile duct cancer, and 50% of lung adenocarcinomas and gastric cancer. The full-length human mesothelin gene encodes the primary product, a 71-kDa precursor protein. The 71-kDa mesothelin precursor is cleaved into two products, 40-kDa C-terminal fragment that remains membrane-bound via glycosylphosphatidylinositol anchor, and a 31-kDa N-terminal fragment, megakaryocyte potentiating factor, which is secreted into the blood. The biological functions of mesothelin remain largely unknown. However, results of recent studies have suggested that the mesothelin may play a role of cell proliferation and migration. In pancreatic cancer, mesothelin expression was immunohistochemically observed in all cases, but absent in normal pancreas and in chronic pancreatitis. Furthermore, the expression of mesothelin was correlated with an poorer patient outcome in several human cancers. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. The present review discusses the expression and function of mesothelin in cancer cells and the utility of mesothelin as a target of cancer therapy.

Keywords: Mesothelin; Luminal membrane expression; Cytoplasmic expression; Tumor marker; Cancer therapy

Core tip: Mesothelin is a 40-kDa cell surface glycoprotein expressed on normal mesothelial cells lining the pleura, pericardium, and peritoneum. Moreover, mesothelin has been shown to be overexpressed in several cancer types. Recent studies have suggested that the overexpression of mesothelin increases cell proliferation and migration. Furthermore, the expression of mesothelin was related to an unfavourable patient outcome in several human cancers. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy.