OBJECTIVES: Lysophosphatidic acid (LPA) is a bioactive lipid mediator involved in tumour progression, cell invasion and metastasis. The mechanism of action of LPA in the invasive and metastatic capacity of human hepatocellular carcinoma (HCC) is not fully understood. This study investigated the effects of LPA on HCC cell invasion and induction of matrix metalloproteinase (MMP) -2 and -9. METHODS: LPA receptor levels in HCC cell lines were detected by Western blot analysis; HCC cell invasion was analysed by the Transwell® system. The LPA receptor blocker Ki16425 was used to determine whether HCC cell invasion was LPA dependent. Expression of the MMP2 and MMP9 genes in HCC cells was determined by real-time quantitative reverse transcription-polymerase chain reaction (qPCR). RESULTS: LPA increased HCC cell invasion, which was LPA-receptor dependent. Real-time RT-qPCR showed that LPA increased MMP9, but not MMP2, expression in HCC cells. Pharmacological inhibition of LPA receptors with Ki16452 significantly attenuated LPA-induced HCC cell invasion. CONCLUSIONS: HCC invasiveness is facilitated by LPA and may be relevant to tumour progression. Thus, LPA receptors may be a potential therapeutic target for HCC.
OBJECTIVES:Lysophosphatidic acid (LPA) is a bioactive lipid mediator involved in tumour progression, cell invasion and metastasis. The mechanism of action of LPA in the invasive and metastatic capacity of humanhepatocellular carcinoma (HCC) is not fully understood. This study investigated the effects of LPA on HCC cell invasion and induction of matrix metalloproteinase (MMP) -2 and -9. METHODS:LPA receptor levels in HCC cell lines were detected by Western blot analysis; HCC cell invasion was analysed by the Transwell® system. The LPA receptor blocker Ki16425 was used to determine whether HCC cell invasion was LPA dependent. Expression of the MMP2 and MMP9 genes in HCC cells was determined by real-time quantitative reverse transcription-polymerase chain reaction (qPCR). RESULTS:LPA increased HCC cell invasion, which was LPA-receptor dependent. Real-time RT-qPCR showed that LPA increased MMP9, but not MMP2, expression in HCC cells. Pharmacological inhibition of LPA receptors with Ki16452 significantly attenuated LPA-induced HCC cell invasion. CONCLUSIONS: HCC invasiveness is facilitated by LPA and may be relevant to tumour progression. Thus, LPA receptors may be a potential therapeutic target for HCC.
Authors: Mohammed A F Elewa; Mohammed M Al-Gayyar; Mona F Schaalan; Khaled H Abd El Galil; Mohamed A Ebrahim; Mamdouh M El-Shishtawy Journal: Clin Exp Metastasis Date: 2015-05-22 Impact factor: 5.150