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.

PubMed Disclaimer

Cited by

The Role of Rho GTPases in VEGF Signaling in Cancer Cells.
El Baba N, Farran M, Khalil EA, Jaafar L, Fakhoury I, El-Sibai M. El Baba N, et al. Anal Cell Pathol (Amst). 2020 Apr 16;2020:2097214. doi: 10.1155/2020/2097214. eCollection 2020. Anal Cell Pathol (Amst). 2020. PMID: 32377503 Free PMC article. Review.
Pertussis Toxin Is a Robust and Selective Inhibitor of High Grade Glioma Cell Migration and Invasion.
Gilder AS, Wang L, Natali L, Karimi-Mostowfi N, Brifault C, Gonias SL. Gilder AS, et al. PLoS One. 2016 Dec 15;11(12):e0168418. doi: 10.1371/journal.pone.0168418. eCollection 2016. PLoS One. 2016. PMID: 27977780 Free PMC article.
Gliosarcoma: distinct molecular pathways and genomic alterations identified by DNA copy number/SNP microarray analysis.
Lowder L, Hauenstein J, Woods A, Chen HR, Rupji M, Kowalski J, Olson JJ, Saxe D, Schniederjan M, Neill S, Weinberg B, Sengupta S. Lowder L, et al. J Neurooncol. 2019 Jul;143(3):381-392. doi: 10.1007/s11060-019-03184-1. Epub 2019 May 9. J Neurooncol. 2019. PMID: 31073965 Free PMC article.
Ion Channels in Glioma Malignancy.
Catacuzzeno L, Sforna L, Esposito V, Limatola C, Franciolini F. Catacuzzeno L, et al. Rev Physiol Biochem Pharmacol. 2021;181:223-267. doi: 10.1007/112_2020_44. Rev Physiol Biochem Pharmacol. 2021. PMID: 32930879 Review.
Serum Metabolomic Profiling of All-Cause Mortality: A Prospective Analysis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study Cohort.
Huang J, Weinstein SJ, Moore SC, Derkach A, Hua X, Liao LM, Gu F, Mondul AM, Sampson JN, Albanes D. Huang J, et al. Am J Epidemiol. 2018 Aug 1;187(8):1721-1732. doi: 10.1093/aje/kwy017. Am J Epidemiol. 2018. PMID: 29390044 Free PMC article.

Role of lysophosphatidic acid and rho in glioma cell motility - PubMed (original) (raw)