Low level of low-density lipoprotein receptor-related protein 1 predicts an unfavorable prognosis of hepatocellular carcinoma after curative resection.
Low level of low-density lipoprotein receptor-related protein 1 predicts an unfavorable prognosis of hepatocellular carcinoma after curative resection.
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BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in receptor-mediated endocytosis and cell signaling.The aim of this study was to elucidate the expression and mechanism ealisboa.com of LRP1 in hepatocellular carcinoma (HCC).METHODS: LRP1 expression in 4 HCC cell lines and 40 HCC samples was detected.
After interruption of LRP1 expression in a HCC cell line either with specific lentiviral-mediated shRNA LRP1 or in the presence of the LRP1-specific chaperone, receptor-associated protein (RAP), the role of LRP1 in the migration and invasion of HCC cells was assessed in vivo and in vitro, and the expression of matrix metalloproteinase (MMP) 9 in cells and the bioactivity of MMP9 in the supernatant were assayed.The expression and prognostic value of LRP1 were investigated in 327 HCC specimens.RESULTS: Low LRP1 expression was associated with poor HCC prognosis, with low expression independently related to shortened overall survival and increased tumor recurrence rate.
Expression of LRP1 in non-recurrent HCC samples was significantly higher than that in early recurrent samples.LRP1 expression in HCC cell lines was inversely correlated with their metastatic potential.After inhibition of LRP1, low-metastatic SMCC-7721 cells showed enhanced migration and invasion and increased expression and bioactivity of MMP9.
Correlation analysis showed a negative correlation between LRP1 and MMP9 expression in HCC patients.The prognostic value of LRP1 expression was validated in the independent data set.CONCLUSIONS: LRP1 modulated the level of MMP9 and low level of LRP1 expression was associated with aggressiveness and invasiveness in HCCs.
LRP1 offered a royal nomadic 5413 rug possible strategy for tumor molecular therapy.