Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells

Lysophosphatidic acid (LPA), which interacts with at least three G protein-coupled receptors (GPCRs), LPA1/Edg-2, LPA2/Edg-4, and LPA3/Edg-7, is a lipid mediator with diverse effects on various cells. Here, we investigated the expression profiles of LPA receptors and patterns of LPA-induced migratio...

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Bibliographic Details
Published in:Experimental cell research 2004-12, Vol.301 (2), p.168-178
Main Authors: Shida, Dai, Kitayama, Joji, Yamaguchi, Hironori, Hama, Kotaro, Aoki, Junken, Arai, Hiroyuki, Yamashita, Hiroharu, Mori, Ken, Sako, Akihiro, Konishi, Tsuyoshi, Watanabe, Toshiaki, Sakai, Teruyuki, Suzuki, Rika, Ohta, Hideo, Takuwa, Yoh, Nagawa, Hirokazu
Format: Article
Language:English
Subjects:
c-Met
Chemotaxis - drug effects
Gastric cancer cell
Gene Expression Profiling
Hepatocyte growth factor
Hepatocyte Growth Factor - pharmacology
Humans
LPA receptor
Lysophosphatidic acid
Lysophospholipids - pharmacology
Migration
Phosphorylation
Proto-Oncogene Proteins c-met - metabolism
Receptors, G-Protein-Coupled - genetics
Receptors, Lysophosphatidic Acid - genetics
RNA, Messenger - analysis
Stomach Neoplasms - pathology
Transactivation
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Summary:Lysophosphatidic acid (LPA), which interacts with at least three G protein-coupled receptors (GPCRs), LPA1/Edg-2, LPA2/Edg-4, and LPA3/Edg-7, is a lipid mediator with diverse effects on various cells. Here, we investigated the expression profiles of LPA receptors and patterns of LPA-induced migration in gastric cancer cells. Northern blot analysis revealed that various gastric cancer cells expressed variable levels of LPA1, LPA2, and LPA3 without a consistent pattern. Using a Boyden chamber assay, LPA markedly increased cell migration of LPA1-expressing cells, the effects of which were almost totally abrogated by Ki16425, an LPA antagonist against LPA1 and LPA3. In contrast, LPA by itself did not significantly induce migration in MKN28 and MKN74 cells, which exclusively expressed LPA2. However, when hepatocyte growth factor (HGF) was placed with LPA in the lower chamber, LPA induced migration of these cells in a dose-dependent manner. Immunoprecipitation analysis revealed that LPA induced transient tyrosine phosphorylation of c-Met in LPA2-expressing cells, which suggests that the transactivation of c-Met by LPA causes a cooperative migratory response with HGF to these cells. Our results indicate that LPA regulates the migration of gastric cancer cells in a receptor-specific manner and suggest that the expression pattern of LPA receptors may affect the metastatic behavior of gastric cancer.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2004.08.008