Differential expression of lysophosphatidic acid receptor-2 in intestinal and diffuse type gastric cancer.
OBJECTIVE
Lysophosphatidic acid (LPA), a natural phospholipid, can modulate diverse cellular responses through LPA receptor, LPA1-4. Although LPA1 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 LPA2 in a various type of cancer, suggesting the positive role of LPA2 in tumor development.


METHODS
We investigated the expression of the LPA2 receptor immunohistochemically in 204 gastric cancers and analyzed the relationship between the expression of LPA2 and clinicopathological features.


RESULTS
LPA2 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 LPA2 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 LPA2 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 LPA2-specific antagonists might have future therapeutic relevance in the treatment as well as prevention of gastric cancer.
Yamashita
Hiroharu
H
Department of Surgical Oncology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. hyamashi-tky@umin.ac.jp
Kitayama
Joji
J
Shida
Dai
D
Ishikawa
Makoto
M
Hama
Kotaro
K
Aoki
Junken
J
Arai
Hiroyuki
H
Nagawa
Hirokazu
H
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism / Q000473:pathology; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D049368:Receptors, Lysophosphatidic Acid / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery
D049368:Receptors, Lysophosphatidic Acid