Lysophosphatidic acid in malignant ascites stimulates migration of human mesenchymal stem cells

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 a...

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Published in:Journal of cellular biochemistry 2008-05, Vol.104 (2), p.499-510
Main Authors: Lee, Mi Jeong, Jeon, Eun Su, Lee, Jung Sub, Cho, Mong, Suh, Dong-Soo, Chang, Chulhun L., Kim, Jae Ho
Format: Article
Language:English
Subjects:
Ascites
Calcium - metabolism
cancer
Cell Movement
Cells, Cultured
Female
Humans
lysophosphatidic acid
Lysophospholipids - physiology
mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
migration
Ovarian Neoplasms - pathology
Peritoneal Neoplasms - pathology
RhoA
rhoA GTP-Binding Protein - metabolism
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Summary: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 LPA1, but not LPA2, 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.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.21641