Lysophosphatidic Acid Is Constitutively Produced by Human Peritoneal Mesothelial Cells and Enhances Adhesion, Migration, and Invasion of Ovarian Cancer Cells

• Juan Ren

  1Department of Cancer Biology, Lerner Research Institute and

• Yi-jin Xiao

  1Department of Cancer Biology, Lerner Research Institute and

• Lisam Shanjukumar Singh

  1Department of Cancer Biology, Lerner Research Institute and

• Xiaoxian Zhao

  1Department of Cancer Biology, Lerner Research Institute and

• Zhenwen Zhao

  1Department of Cancer Biology, Lerner Research Institute and

• Li Feng

  3Echelon Biosciences, Inc.; and

• Tyler M. Rose

  4Department of Medicinal Chemistry, The University of Utah, Salt Lake City, Utah

• Glenn D. Prestwich

  4Department of Medicinal Chemistry, The University of Utah, Salt Lake City, Utah

• Yan Xu

  1Department of Cancer Biology, Lerner Research Institute and

抄録

Lysophosphatidic acid (LPA) is both a potential marker and a therapeutic target for ovarian cancer. It is critical to identify the sources of elevated LPA levels in ascites and blood of patients with ovarian cancer. We show here that human peritoneal mesothelial cells constitutively produce LPA, which accounts for a significant portion of the chemotactic activity of the conditioned medium from peritoneal mesothelial cells to ovarian cancer cells. Both production of LPA by peritoneal mesothelial cells and the chemotactic activity in the conditioned medium can be blocked by HELSS [an inhibitor of the calcium-independent phospholipase A2 (iPLA2)] and AACOCF3 [an inhibitor of both cytosolic PLA2 (cPLA2) and iPLA2]. Moreover, cell-based enzymatic activity assays for PLA2 indicate that peritoneal mesothelial cells have strong constitutive PLA2 activity. Receptors for LPA, LPA2, and LPA3 are involved in the conditioned medium–induced chemotactic activity. Invasion of ovarian cancer cells into peritoneal mesothelial cells has also been analyzed and shown to require PLA2, LPA receptors, and the mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase signaling pathway. Thus, we show here, for the first time, that human peritoneal mesothelial cells constitutively produce bioactive lipid signaling molecules, such as LPA, via iPLA2 and/or cPLA2 activities. Conditioned medium from peritoneal mesothelial cells stimulate migration, adhesion, and invasion of ovarian cancer cells, and may play similar roles in vivo. (Cancer Res 2006; 66(6): 3006-14)

収録刊行物

• Cancer Research

  Cancer Research 66 (6), 3006-3014, 2006-03-15

  American Association for Cancer Research (AACR)

キーワード

• Cancer Research
• Oncology

詳細情報

• CRID: 1364233268378575744
• NII論文ID: 30018588019
• DOI: 10.1158/0008-5472.can-05-1292
• ISSN: 15387445
• ISSN: 00085472
• Web Site: https://aacrjournals.org/cancerres/article-pdf/66/6/3006/2559243/3006.pdf
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