| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cell, Tumor, and Stem Cell Biology |
1 Department of Cancer Biology, Lerner Research Institute and 2 Department of Gynecology and Obstetrics, The Cleveland Clinic Foundation, Cleveland, Ohio; 3 Echelon Biosciences, Inc.; and 4 Department of Medicinal Chemistry, The University of Utah, Salt Lake City, Utah
Requests for reprints: Yan Xu, Department of Obstetrics and Gynecology, Indiana University, 975 W. Walnut St. IB355A, Indianapolis, IN 46202. Fax: 317-278-2884; E-mail: Xu2{at}iupui.edu.
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 mediuminduced 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)
This article has been cited by other articles:
![]() |
D. Wang, Z. Zhao, A. Caperell-Grant, G. Yang, S. C. Mok, J. Liu, R. M. Bigsby, and Y. Xu S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells Mol. Cancer Ther., July 1, 2008; 7(7): 1993 - 2002. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Ptaszynska, M. L. Pendrak, R. W. Bandle, M. L. Stracke, and D. D. Roberts Positive Feedback between Vascular Endothelial Growth Factor-A and Autotaxin in Ovarian Cancer Cells Mol. Cancer Res., March 1, 2008; 6(3): 352 - 363. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Said, M. J. Socha, J. J. Olearczyk, A. A. Elmarakby, J. D. Imig, and K. Motamed Normalization of the Ovarian Cancer Microenvironment by SPARC Mol. Cancer Res., October 1, 2007; 5(10): 1015 - 1030. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Zhao, Y. Xiao, P. Elson, H. Tan, S. J. Plummer, M. Berk, P. P. Aung, I. C. Lavery, J. P. Achkar, L. Li, et al. Plasma Lysophosphatidylcholine Levels: Potential Biomarkers for Colorectal Cancer J. Clin. Oncol., July 1, 2007; 25(19): 2696 - 2701. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Zhao, D. Wang, Z. Zhao, Y. Xiao, S. Sengupta, Y. Xiao, R. Zhang, K. Lauber, S. Wesselborg, L. Feng, et al. Caspase-3-dependent Activation of Calcium-independent Phospholipase A2 Enhances Cell Migration in Non-apoptotic Ovarian Cancer Cells J. Biol. Chem., September 29, 2006; 281(39): 29357 - 29368. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Tsuda, S. Okudaira, K. Moriya-Ito, C. Shimamoto, M. Tanaka, J. Aoki, H. Arai, K. Murakami-Murofushi, and T. Kobayashi Cyclic Phosphatidic Acid Is Produced by Autotaxin in Blood J. Biol. Chem., September 8, 2006; 281(36): 26081 - 26088. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.-S. Kim, S. Sengupta, M. Berk, Y.-G. Kwak, P. F. Escobar, J. Belinson, S. C. Mok, and Y. Xu Hypoxia Enhances Lysophosphatidic Acid Responsiveness in Ovarian Cancer Cells and Lysophosphatidic Acid Induces Ovarian Tumor Metastasis In vivo Cancer Res., August 15, 2006; 66(16): 7983 - 7990. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |