Transient receptor potential vanilloid-type 2 targeting on stemness in liver cancer - 11/07/18
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Graphical abstract |
TRPV2 exerts effect on the acquisition of the stemness of liver cancer cells. An increase of the spheroid and colony formation was noted by ablation of TRPV2 in HepG2 cells accompanied with upregulations of cancer stem cell markers including CD133, CD44 and ALDH1 by treatment of TRPV2 shRNA or Tranilast. On the contrary, a decrease of the stemness of SMMC-7721 cells was observed by administration of the TRPV2 cDNA or Probenecid.
Highlights |
• | TRPV2 expression is negatively associated with the stemness of liver cancer cell lines. |
• | Alternation of TRPV2 expression significantly affects liver cancer stem cells and xenograft growth. |
• | Activation of TRPV2 is a potential promising strategy targeting for stemness to cure human liver cancer. |
Abstract |
The malignant phenotype of the cells resulting from human liver cancer is driven by liver cancer stem-like cells (LCSLCs). Transient Receptor Potential Vanilloid-type 2 channel (TRPV2) contributes to the progression of different tumor types, including liver cancer. In the current study, the TRPV2 expression levels give rise to the effect on stemness in liver cancer cell lines. TRPV2 knockdown in HepG2 cells enhanced spheroid and colony formation, and expression levels of CD133, CD44 and ALDH1 whereas the opposite effects were observed in TRPV2 enforced expression in SMMC-7721 cells. Furthermore, TRPV2 overexpression restored inhibition of spheroid and colony formation, and stem cell markers expression in HepG2 cells with TRPV2 silencing. The addition of the TRPV2 agonist probenecid and the TRPV2 antagonist tranilast suppressed and/or increased in vitro spheroid and colony formation, and stem cell marker expression of LCSLCs and/or liver cancer cell lines, respectively. Notably, probenecid and tranilast significantly inhibited or promoted tumor growth of HepG2 xenografts in the severe combined immunodeficiency (SCID) mouse model, respectively. TRPV2 expression at protein levels revealed converse correlation with those of CD133 and CD44 in human hepatocellular carcinoma (HCC) tissue. Collectively, the data demonstrate that TRPV2 exert effects on stemness of liver cancer and is a potential target in the treatment of human liver cancer patients.
Le texte complet de cet article est disponible en PDF.Abbreviations : HHC, LCSLC, TRPV2, TRP, SCID, ALDH1, GFP, LPL, CAPE, hrbFGF, hrEGF, TRPC, TRPM, TRPV, JNK1, MRP, ABCC2, MRP4, CSC, DMEM
Keywords : Liver cancer, Liver cancer stem cell, Transient receptor potential vanilloid-type 2 channel, Probenecid, Tranilast, Self-renewal
Plan
Vol 105
P. 697-706 - septembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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