Abstract
Sarcomatoid hepatocellular carcinoma (SHC) is a rare type of HCC with significantly poorer survival than ordinary HCC. Little is known about the mechanism associated with SHC and its biomarkers and therapy. Here, we established a mouse liver cancer cell line and designated as Ymac-1. A sarcomatous appearance was observed in the allograft tumor arose from Ymac-1. Liver-secreted plasma proteins were found in Ymac-1 cultured supernatant by proteomics analysis. The positive staining of CK7, CK8, Vimentin and the suppressed expression of AFP indicated that Ymac-1 is a SHC cell line. Compared to its original tumor, an elevated level of EMT markers, N-cadherin and Vimentin, was found in Ymac-1. Ymac-1 displayed a higher migration rate and side population percentage than a mouse ordinary HCC cell line-Hepa1-6. Microarray analysis was performed to identify potential biomarkers/therapeutic targets for SHC. G6pd, a vital enzyme in pentose phosphate pathway, is highly expressed in Ymac-1. Depletion of G6pd in Ymac-1 reduced CD133 expression and sphere formation. Positive correlations between G6PD and CD133 were observed in human specimen. Higher expression of both G6PD and CD133 in tumor were associated with poor survival. In summary Ymac-1 can be a useful SHC cell model for novel biomarker and therapy development.
Highlights
IntroductionSarcomatoid dedifferentiation of cancer cells (carcinomas with spindle-cell components) is one of the interesting histopathologic features of carcinomas[1, 2]
Sarcomatoid dedifferentiation of cancer cells is one of the interesting histopathologic features of carcinomas[1, 2]
Further studies demonstrated that Ymac-1 cells displayed epithelial–mesenchymal transition (EMT) phenotypes and contained a substantial population that possessed cancer stem cells (CSCs)-like properties, which resemble the clinical observations of sarcomatoid hepatocellular carcinoma (HCC)
Summary
Sarcomatoid dedifferentiation of cancer cells (carcinomas with spindle-cell components) is one of the interesting histopathologic features of carcinomas[1, 2]. It has been proposed that sarcomatoid cells in liver cancers are originated from trans-differentiation of HCC or cholangiocarcinoma[12, 13]. Due to the heterogeneity nature of liver cancer, it is difficult to distinguish SHC from ordinary HCC on imaging findings alone. It is reasonable to hypothesize that liver tumor from Gnmt−/− mice should be composed of heterogeneous cell population containing stem cell/progenitor cell-like subpopulation. We established a cancer cell line from the liver tumor of Gnmt−/− mice and designated it as Ymac-1 cell. The positive staining of CK8 and suppressed expression of AFP indicated Ymac-1 cell is a sarcomatoid HCC cell line. Ymac-1 cell expressed EMT markers and possessed cancer stem cell-like properties. Ymac-1 cell could be an excellent model for SHC research and may shed light on the prevention, diagnosis and treatment of SHC
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