LPA receptor 2 mediates LPA-induced endometrial cancer invasion

Hope, Joanie Mayer; Wang, Feng qiang; Whyte, Jill; Ariztia, Edgardo V.; Abdalla, Walid; Long, K.; Fishman, David A.

doi:10.1016/j.ygyno.2008.09.019

Cited by 39 publications

(28 citation statements)

References 54 publications

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“…LPAR1 has been found to induce migration in cells from breast cancer [48], pancreatic cancer [49], and hepatocellular carcinoma [50] while it inhibited metastasis and invasion in prostate organotypic models [51]. LPAR2 was found to mediate LPA-induced invasion in endometrial cancer [52], but seemed to have an inhibitory role in pancreatic cancer [49]. In breast carcinoma cells both LPAR1 and 2 mediated LPA-induced migration, where LPAR1 worked at lower LPA-concentrations than LPAR2 and thus contributed to an effect over wider concentration ranges [53].…”

Section: Discussionmentioning

confidence: 99%

Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous carcinoma cells

et al. 2014

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BackgroundOral squamous cell carcinoma is an aggressive neoplasm with serious morbidity and mortality, which typically spreads through local invasive growth. Lysophosphatidic acid (LPA) is involved in a number of biological processes, and may have a role in cancer cell migration and invasiveness. LPA is present in most tissues and can activate cells through six different LPA receptors (LPAR1-6). Although LPA is predominantly promigratory, some of the receptors may have antimigratory effects in certain cells. The signalling mechanisms of LPA are not fully understood, and in oral carcinoma cells the specific receptors and pathways involved in LPA-stimulated migration are unknown.MethodsThe oral carcinoma cell lines E10, SCC-9, and D2 were investigated. Cell migration was studied in a scratch wound assay, and invasion was demonstrated in organotypic three dimensional co-cultures. Protein and mRNA expression of LPA receptors was studied with Western blotting and qRT-PCR. Activation of signalling proteins was examined with Western blotting and isoelectric focusing, and signalling mechanisms were further explored using pharmacological agents and siRNA directed at specific receptors and pathways.ResultsLPA stimulated cell migration in the two oral carcinoma cell lines E10 and SCC-9, but was slightly inhibitory in D2. The receptor expression profile and the effects of specific pharmacological antagonist and agonists indicated that LPA-stimulated cell migration was mediated through LPAR3 in E10 and SCC-9. Furthermore, in both these cell lines, the stimulation by LPA was dependent on PKC activity. However, while LPA induced transactivation of EGFR and the stimulated migration was blocked by EGFR inhibitors in E10 cells, LPA did not induce EGFR transactivation in SCC-9 cells. In D2 cells, LPA induced EGFR transactivation, but this was associated with slowing of a very high inherent migration rate in these cells.ConclusionThe results demonstrate LPA-stimulated migration in oral carcinoma cells through LPAR3, mediated further by PKC, which acts either in concert with or independently of EGFR transactivation.

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Section: Discussionmentioning

confidence: 99%

Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous carcinoma cells

et al. 2014

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“…In particular, LPA 2 overexpression has been observed in several cancers in vivo and in vitro (287,288). LPA 2 signaling has been associated with invasion and metastasis of ovarian, endometrial, mesothelioma, and colon cancer cells (289,290), likely through the activation and induction of VEGF, EGFR, metalloproteinases, urokinase-type plasminogen activator, cyclooxygenase-2, vitro and in a mouse xenograft model (195). The treated cancer cells demonstrated reduced migration, inhibition of cancer cell invasion, tumor regression, and decreased blood vessel density surrounding the tumor.…”

Section: Cancermentioning

confidence: 99%

LPA receptor signaling: pharmacology, physiology, and pathophysiology

Yung

Stoddard

Chun

2014

Journal of Lipid Research

597

683

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“…LPA 1 controls MMP-9 secretion that induces the invasion of human hepatocellular carcinoma cells [27]. Other LPA receptors might also regulate the secretion of other MPPs such as MMP-7 via LPA 2 in ovarian cancer cells [28]. Using B16 cells as a model for melanoma, the group of W. Moolenaar showed that LPA and serum almost completely inhibit the transwell B16 cell migration [29].…”

Section: Involvement Of Lpa Receptors In Cancermentioning

confidence: 99%