Expression and function of lysophosphatidic acid receptors (LPARs) 1 and 3 in human hepatic cancer progenitor cells

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作者：

Z Valentina，S Eugene，JH Swet，WA Ahrens，S Victor，DA Iannitti，IH Mckillop

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摘要：

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and is characterized by rapid tumor expansion and metastasis. Lysophosphatidic acid (LPA) signaling,viaLPA receptors 1–6 (LPARs1–6), regulates diverse cell functions including motility, migration, and proliferation, yet the role of LPARs in hepatic tumor pathology is poorly understood. We sought to determine the expression and function of endothelial differentiation gene (EDG) LPARs (LPAR1–3) in human HCC and complimentaryin vitromodels. Human HCC were characterized by significantly elevated LPAR1/LPAR3 expression in the microenvironment between the tumor and non-tumor liver (NTL), a finding mirrored in human SKHep1 cells. Analysis of human tissue and human hepatic tumor cellsin vitrorevealed cells that express LPAR3 (HCC-NTL marginin vivoand SKHep1in vitro) also express cancer stem cell markers in the absence of hepatocyte markers. Treatment of SKHep1 cells with exogenous LPA led to significantly increased cell motility but not proliferation. Using pharmacological agents and cells transfected to knock-down LPAR1 or LPAR3 demonstrated LPA-dependent cell migration occursviaan LPAR3-Gi-ERK-pathway independent of LPAR1. These data suggest cells that stain positive for both LPAR3 and cancer stem cell markers are distinct from the tumor massper se, and may mediate tumor invasiveness/expansion via LPA-LPAR3 signaling.

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关键词：

lysophosphatidic acid (LPA hepatocellular carcinoma (HCC SKHep1 cell migration Gi-protein

DOI：

10.18632/oncotarget.6696

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年份：

2016