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Lysophosphatidic acid in malignant ascites stimulates migration of human mesenchymal stem cells
Author(s) -
Lee Mi Jeong,
Jeon Eun Su,
Lee Jung Sub,
Cho Mong,
Suh DongSoo,
Chang Chulhun L.,
Kim Jae Ho
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21641
Subject(s) - lysophosphatidic acid , mesenchymal stem cell , pertussis toxin , rhoa , cancer research , cell migration , chemistry , rho kinase inhibitor , biology , kinase , endocrinology , microbiology and biotechnology , medicine , rho associated protein kinase , cell , receptor , signal transduction , g protein , biochemistry
Lysophosphatidic acid (LPA) is elevated in ascites of ovarian cancer patients and is involved in growth and invasion of ovarian cancer cells. Accumulating evidence suggests a pivotal role of mesenchymal stem cells (MSCs) or stromal cells in tumorigenesis. In the present study, we demonstrated that ascites from ovarian cancer patients and LPA increased migration of human MSCs. The migration of MSCs induced by LPA and malignant ascites was completely abrogated by pretreatment with Ki16425, an antagonist of LPA receptors, and by silencing of endogenous LPA 1 , but not LPA 2 , with small interference RNA, suggesting a key role of LPA played in the malignant ascites‐induced migration. LPA induced activation of ERK through pertussis toxin‐sensitive manner, and pretreatment of MSCs with U0126, a MEK inhibitor, or pertussis toxin attenuated the LPA‐induced migration. Moreover, LPA induced activation of RhoA in MSCs, and pretreatment of the cells with Y27632, a Rho kinase inhibitor, markedly inhibited the LPA‐induced migration. In addition, LPA and malignant ascites increased intracellular concentration of calcium in MSCs, and Ki16425 completely inhibited the elevation of intracellular calcium. These results suggest that LPA is a crucial component of the malignant ascites which induce the migration of MSCs and elevation of intracellular calcium. J. Cell. Biochem. 104: 499–510, 2008. © 2007 Wiley‐Liss, Inc.