Journal
EXPERIMENTAL AND MOLECULAR MEDICINE
Volume 40, Issue 6, Pages 607-616Publisher
NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2008.40.6.607
Keywords
cell movement; cyclooxygenase-2; lysophosphatidic acid; ovarian neoplasms; proto-oncogene proteins pp60 (c-src); receptors, lysophosphatidic acid
Funding
- Korea Science and Engineering Fund through the Cancer Metastasis Research Center (CMRC) at Yonsei University
- Korea Food and Drug Administration [08172-KFDA518]
- Konyang University Myunggok Medical Research Fund
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Lysophosphatidic acid (LPA) is a bioactive phospholipids and involves in various cellular events, including tumor cell migration. In the present study, we investigated LPA receptor and its transactivation to EGFR for cyclooxygenase-2 (COX-2) expression and cell migration in CAOV-3 ovarian cancer cells. LPA induced COX-2 expression in a dose-dependent manner, and pretreatment of the cells with pharmacological inhibitors of Gi (pertussis toxin), Src (PP2), EGF receptor (EGFR) (AG1478), ERK (PD98059) significantly inhibited LPA-induced COX-2 expression. Consistent to these results, transfection of the cells with selective Src siRNA attenuated COX-2 expression by LPA. LPA stimulated CAOV-3 cell migration that was abrogated by pharmacological inhibitors and antibody of EP2. Higher expression of LPA2 mRNA was observed in CAOV-3 cells, and transfection of the cells with a selective LPA2 siRNA significantly inhibited LPA-induced activation of EGFR and ERK, as well as COX-2 expression. Importantly, LPA2 siRNA also blocked LPA-induced ovarian cancer cell migration. Collectively, our results clearly show the significance of LPA2 and Gi/Src pathway for LPA-induced COX-2 expression and cell migration that could be a promising drug target for ovarian cancer cell metastasis.
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