Role of lysophosphatidic acid and rho in glioma cell motility - PubMed (original) (raw)
Role of lysophosphatidic acid and rho in glioma cell motility
T J Manning Jr et al. Cell Motil Cytoskeleton. 2000 Mar.
Abstract
We have studied the effects of the bioactive phospholipid lysophosphatidic acid (LPA) on cell lines derived from highly invasive human glioblastoma multiforme (GBM). Using transwell migration assays, we show that LPA stimulates both chemokinetic and chemotactic migration of glioma cells. Blood brain barrier breakdown and leakage of serum components that most likely include LPA are common features of GBM. Therefore, the effects of LPA on glioma cell motility are intriguing given the fact that, in vivo, GBM cells often migrate great distances from the main tumor, rendering successful therapy extremely difficult. We show here that LPA initiates a variety of signaling cascades in glioma cells. LPA-enhanced transwell migration was sensitive to pertussis toxin (PTX) treatment suggesting an important role for G(i) subtype of G proteins. LPA also stimulated Ca(2+) fluctuations and activation of extracellular signal-regulated kinases (ERKS) 1 and 2, although blocking either pathway had little effect on glioma cell migration. Exposure of glioma cells to LPA resulted in phosphorylation of the regulatory light chain (RLC) of myosin II and the formation of stress fibers and focal adhesions. These effects were blocked by Y-27632, an inhibitor of Rho-activated ROCK kinases. Time-lapse video microscopy revealed that Y-27632-treatment caused cells to assume long thin morphologies that suggested deficiencies in the contractile apparatus. Furthermore, many cells exhibited a conspicuous extension of processes when Rho/ROCK kinase cascades were inhibited. The above results suggest that LPA/Rho signaling cascades play important roles in glioma cell motility and that exposure of tumor cells to LPA in vivo may contribute to their invasive phenotype.
Copyright 2000 Wiley-Liss, Inc.
Similar articles
- Rho/ROCK and MAPK signaling pathways are involved in glioblastoma cell migration and proliferation.
Zohrabian VM, Forzani B, Chau Z, Murali R, Jhanwar-Uniyal M. Zohrabian VM, et al. Anticancer Res. 2009 Jan;29(1):119-23. Anticancer Res. 2009. PMID: 19331140 - The G protein-coupled receptor S1P2 regulates Rho/Rho kinase pathway to inhibit tumor cell migration.
Lepley D, Paik JH, Hla T, Ferrer F. Lepley D, et al. Cancer Res. 2005 May 1;65(9):3788-95. doi: 10.1158/0008-5472.CAN-04-2311. Cancer Res. 2005. PMID: 15867375 - Lysophosphatidic acid regulates the proliferation and migration of olfactory ensheathing cells in vitro.
Yan H, Lu D, Rivkees SA. Yan H, et al. Glia. 2003 Oct;44(1):26-36. doi: 10.1002/glia.10265. Glia. 2003. PMID: 12951654 - The regulatory roles of ROCK and MRCK kinases in the plasticity of cancer cell migration.
Kale VP, Hengst JA, Desai DH, Amin SG, Yun JK. Kale VP, et al. Cancer Lett. 2015 Jun 1;361(2):185-96. doi: 10.1016/j.canlet.2015.03.017. Epub 2015 Mar 18. Cancer Lett. 2015. PMID: 25796438 Review.
Cited by
- Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production.
Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Arai H. Umezu-Goto M, et al. J Cell Biol. 2002 Jul 22;158(2):227-33. doi: 10.1083/jcb.200204026. Epub 2002 Jul 15. J Cell Biol. 2002. PMID: 12119361 Free PMC article. - Metabolomic Profiling of Serum Retinol in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.
Huang J, Panagiotou OA, Anic GM, Mondul AM, Liao LM, Derkach A, Stolzenberg-Solomon R, Weinstein SJ, Albanes D. Huang J, et al. Sci Rep. 2017 Sep 6;7(1):10601. doi: 10.1038/s41598-017-09698-w. Sci Rep. 2017. PMID: 28878287 Free PMC article. - Lipid Phosphate Phosphatases and Cancer.
Tang X, Brindley DN. Tang X, et al. Biomolecules. 2020 Sep 2;10(9):1263. doi: 10.3390/biom10091263. Biomolecules. 2020. PMID: 32887262 Free PMC article. Review. - Ion channels and amino acid transporters support the growth and invasion of primary brain tumors.
Sontheimer H. Sontheimer H. Mol Neurobiol. 2004 Feb;29(1):61-71. doi: 10.1385/MN:29:1:61. Mol Neurobiol. 2004. PMID: 15034223 Free PMC article. Review. - Lysophosphatidic acid signaling in airway epithelium: role in airway inflammation and remodeling.
Zhao Y, Natarajan V. Zhao Y, et al. Cell Signal. 2009 Mar;21(3):367-77. doi: 10.1016/j.cellsig.2008.10.010. Epub 2008 Oct 26. Cell Signal. 2009. PMID: 18996473 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous