LPA-induced epithelial ovarian cancer (EOC) in vitro invasion and migration are mediated by VEGF receptor-2 (VEGF-R2)
- PMID: 15919106
- DOI: 10.1016/j.ygyno.2005.03.004
LPA-induced epithelial ovarian cancer (EOC) in vitro invasion and migration are mediated by VEGF receptor-2 (VEGF-R2)
Abstract
Objective: Lysophosphatidic acid (LPA) stimulates ovarian tumor growth partially via induction of VEGF expression through transcriptional activation. Previous studies have shown that LPA induces epithelial ovarian cancer (EOC) in vitro metastasis. In this study, we examined the role of VEGF in LPA-induced EOC invasion and migration and underlying mechanisms.
Methods: The invasiveness of DOV13 cells was determined by in vitro basement membrane Matrigel invasion assay. Ovarian carcinoma cellular migration was quantified by the colloidal gold migration assay. Matrix metalloproteinase (MMP)-2 secretion and activation were detected by gelatin zymography. Urokinase type plasminogen activator (uPA) activity was determined by a coupled colorimetric assay measuring the activity of generated plasmin. Student's t test and one-way ANOVA were used for statistical analysis.
Results: Using a VEGF neutralizing monoclonal antibody (mAb), we show that LPA-induced EOC invasion is dependent upon VEGF. Using the selective VEGF receptor (VEGFR)-2 inhibitor, SU1498, LPA-induced EOC invasion and migration were significantly inhibited in a concentration-dependent manner. In addition, SU1498 inhibits MMP-2 secretion and uPA activity in ovarian cancer DOV13 cells. At 5 and 20 microM, SU1498 almost completely inhibited the activity of MMP-2 and uPA. SU1498 also decreases the LPA-induced increase of uPA activity in DOV13 cells.
Conclusions: Our results show that LPA-induced EOC invasion is at least partially mediated by VEGF. Further, the VEGFR-2-mediated signaling transduction pathway may be involved in LPA-induced EOC invasion and migration by regulating the secretion and activation of MMP-2 and uPA.
Similar articles
-
The NF-κB pathway mediates lysophosphatidic acid (LPA)-induced VEGF signaling and cell invasion in epithelial ovarian cancer (EOC).Gynecol Oncol. 2011 Oct;123(1):129-37. doi: 10.1016/j.ygyno.2011.06.006. Epub 2011 Jul 22. Gynecol Oncol. 2011. PMID: 21782227
-
Vascular endothelial growth factor-regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases.Int J Cancer. 2006 Feb 15;118(4):879-88. doi: 10.1002/ijc.21421. Int J Cancer. 2006. PMID: 16152587
-
VEGFR-2 silencing by small interference RNA (siRNA) suppresses LPA-induced epithelial ovarian cancer (EOC) invasion.Gynecol Oncol. 2009 Dec;115(3):414-23. doi: 10.1016/j.ygyno.2009.08.019. Epub 2009 Sep 18. Gynecol Oncol. 2009. PMID: 19765808
-
Osteopontin: it's role in regulation of cell motility and nuclear factor kappa B-mediated urokinase type plasminogen activator expression.IUBMB Life. 2005 Jun;57(6):441-7. doi: 10.1080/15216540500159424. IUBMB Life. 2005. PMID: 16012053 Review.
-
[Mechanism of tumor cell-induced extracellular matrix degradation--inhibition of cell-surface proteolytic activity might have a therapeutic effect on tumor cell invasion and metastasis].Nihon Sanka Fujinka Gakkai Zasshi. 1996 Aug;48(8):623-32. Nihon Sanka Fujinka Gakkai Zasshi. 1996. PMID: 8808830 Review. Japanese.
Cited by
-
Metabolic reprogramming of the tumor immune microenvironment in ovarian cancer: A novel orientation for immunotherapy.Front Immunol. 2022 Oct 14;13:1030831. doi: 10.3389/fimmu.2022.1030831. eCollection 2022. Front Immunol. 2022. PMID: 36311734 Free PMC article. Review.
-
Doxycycline attenuates breast cancer related inflammation by decreasing plasma lysophosphatidate concentrations and inhibiting NF-κB activation.Mol Cancer. 2017 Feb 8;16(1):36. doi: 10.1186/s12943-017-0607-x. Mol Cancer. 2017. PMID: 28178994 Free PMC article.
-
Anti-tumour activity of tivozanib, a pan-inhibitor of VEGF receptors, in therapy-resistant ovarian carcinoma cells.Sci Rep. 2017 Apr 6;7:45954. doi: 10.1038/srep45954. Sci Rep. 2017. PMID: 28383032 Free PMC article.
-
Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo.J Biomed Res. 2016 Jul;30(4):272-84. doi: 10.7555/JBR.30.20150058. Epub 2015 Aug 28. J Biomed Res. 2016. PMID: 27533936 Free PMC article. Review.
-
Role of Adipose Tissue-Derived Autotaxin, Lysophosphatidate Signaling, and Inflammation in the Progression and Treatment of Breast Cancer.Int J Mol Sci. 2020 Aug 18;21(16):5938. doi: 10.3390/ijms21165938. Int J Mol Sci. 2020. PMID: 32824846 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous