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Differential expression of lysophosphatidic acid receptor‐2 in intestinal and diffuse type gastric cancer
Author(s) -
Yamashita Hiroharu,
Kitayama Joji,
Shida Dai,
Ishikawa Makoto,
Hama Kotaro,
Aoki Junken,
Arai Hiroyuki,
Nagawa Hirokazu
Publication year - 2005
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20397
Subject(s) - lysophosphatidic acid , cancer , medicine , cancer research , carcinogenesis , receptor , receptor expression , metastasis , cancer cell , tumor progression , pathology
Abstract Background and Objectives Lysophosphatidic acid (LPA), a natural phospholipid, can modulate diverse cellular responses through LPA receptor, LPA 1–4 . Although LPA 1 is known to be widely expressed in human tissues, the distribution of other LPA receptors is not characterized in malignant tissues. Recently, it was reported that malignant transformation resulted in aberrant expression of LPA 2 in a various type of cancer, suggesting the positive role of LPA 2 in tumor development. Methods We investigated the expression of the LPA 2 receptor immunohistochemically in 204 gastric cancers and analyzed the relationship between the expression of LPA 2 and clinicopathological features. Results LPA 2 was preferentially expressed (67%) in intestinal‐type cancer that was significantly higher than that in diffuse‐type cancer (32%, P < 0.0001). The expression of LPA 2 showed correlation with a higher rate of lymphatic and venous invasion, lymphatic metastasis, and resultingly tumor stage in diffuse‐type cancer, but not in intestinal‐type cancer. Conclusions Our results highlight the possibility that LPA 2 expression is an important process in the carcinogenesis of gastric cancer, especially in intestinal‐type cancer. Since LPA can transactivate HGF receptor (c‐Met) as well as EGF‐receptor, LPA may promote the progression of gastric cancer in diffuse‐type with high expression of c‐Met. The development of LPA 2 ‐specific antagonists might have future therapeutic relevance in the treatment as well as prevention of gastric cancer. J. Surg. Oncol. 2006;93:30–35. © 2005 Wiley‐Liss, Inc.