HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Chen, M. Articles by O'Connor, K. L. Search for Related Content PubMed PubMed Citation Articles by Chen, M. Articles by O'Connor, K. L.

RECEPTORS AND SIGNAL TRANSDUCTION

LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells

Department of Surgery and the Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas

Submitted 24 July 2006 ; accepted in final form 11 December 2006

Lysophosphatidic acid (LPA) acts via binding to specific G protein-coupled receptors and has been implicated in the biology of breast cancer. Here, we characterize LPA receptor expression patterns in common established breast cancer cell lines and their contribution to breast cancer cell motility. By measuring expression of the LPA receptors LPA1, LPA2, and LPA3 with real-time quantitative PCR, we show that the breast cancer cell lines tested can be clustered into three main groups: cells that predominantly express LPA1 (BT-549, Hs578T, MDA-MB-157, MDA-MB-231, and T47D), cells that predominantly express LPA2 (BT-20, MCF-7, MDA-MB-453, and MDA-MB-468), and a third group that shows comparable expression level of these two receptors (MDA-MB-175 and MDA-MB-435). LPA3 expression was detected primarily in MDA-MB-157 cells. Using a Transwell chemotaxis assay to monitor dose response, we find that cells predominantly expressing LPA1 have a peak migration rate at 100 nM LPA that drops off dramatically at 1 µM LPA, whereas cells predominantly expressing LPA2 show the peak migration rate at 1 µM LPA, which remains high at 10 µM. Using BT-20 cells, LPA2-specific small interfering RNA, and C3 exotransferase, we demonstrate that LPA2 can mediate LPA-stimulated cell migration and activation of the small GTPase RhoA. Using LPA2 small interfering RNA, exogenous expression of LPA1, and treatment with Ki16425 LPA receptor antagonist in the BT-20 cells, we further find that LPA1 and LPA2 cooperate to promote LPA-stimulated chemotaxis. In summary, our results suggest that the expression of both LPA1 and LPA2 may contribute to chemotaxis and may permit cells to respond optimally to a wider range of LPA concentrations, thus revealing a new aspect of LPA signaling.

G protein-coupled receptor; lysophosphatidic acid; chemotactic migration; GTPase

This article has been cited by other articles:

				X. Ye Lysophospholipid signaling in the function and pathology of the reproductive system Hum. Reprod. Update, September 1, 2008; 14(5): 519 - 536. [Abstract] [Full Text] [PDF]

				C. E. Horak, A. Mendoza, E. Vega-Valle, M. Albaugh, C. Graff-Cherry, W. G. McDermott, E. Hua, M. J. Merino, S. M. Steinberg, C. Khanna, et al. Nm23-H1 Suppresses Metastasis by Inhibiting Expression of the Lysophosphatidic Acid Receptor EDG2 Cancer Res., December 15, 2007; 67(24): 11751 - 11759. [Abstract] [Full Text] [PDF]