TY - JOUR
T1 - Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells
AU - Shida, Dai
AU - Kitayama, Joji
AU - Yamaguchi, Hironori
AU - Hama, Kotaro
AU - Aoki, Junken
AU - Arai, Hiroyuki
AU - Yamashita, Hiroharu
AU - Mori, Ken
AU - Sako, Akihiro
AU - Konishi, Tsuyoshi
AU - Watanabe, Toshiaki
AU - Sakai, Teruyuki
AU - Suzuki, Rika
AU - Ohta, Hideo
AU - Takuwa, Yoh
AU - Nagawa, Hirokazu
PY - 2004/12/10
Y1 - 2004/12/10
N2 - 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.
AB - 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.
KW - Gastric cancer cell
KW - Hepatocyte growth factor
KW - LPA receptor
KW - Lysophosphatidic acid
KW - Migration
KW - Transactivation
KW - c-Met
UR - http://www.scopus.com/inward/record.url?scp=8644287634&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8644287634&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2004.08.008
DO - 10.1016/j.yexcr.2004.08.008
M3 - Article
C2 - 15530853
AN - SCOPUS:8644287634
VL - 301
SP - 168
EP - 178
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 2
ER -
