It also generates compensatory liver regeneration and DNA hypermethylation in some genes. Anti-oxidative therapy prevents HCC without attenuating apoptosis, regeneration and methylation status. Disclosures: Tetsuo Takehara – Grant/Research Support: Chugai Pharmaceutical
Co., MSD K.K. The following people have nothing to disclose: Hayato Hikita, Tomohide find more Tatsumi, Yoshinobu Saito, Satoshi Tanaka, Satoshi Shimizu, Wei Li, Ryotaro Sakamori, Takuya Miyagi, Naoki Hiramatsu [Background] Cancer stem cells (CSCs) are considered a pivotal target for the eradication of hepatocellular carcinoma (HCC). We recently reported that CSC markers EpCAM and CD90 are independently expressed in primary HCCs and cell lines and that CD90+ cells share features of metastatic vascular endothelial cells and express the vascular endothelial marker CD105, a co-receptor of transforming growth factor beta (Yamashita T, et al Hepatology 2013). In this study, we evaluated the effect of cytotoxic reagents on the expression of CD1 05 in human HCC. [Methods] Primary HCC cells obtained from surgically resected specimens and EpCAM+ CD90- cell lines Huh1 and Huh7 were treated with 5-FU or epirubicin in vitro. Gene and protein expression was evaluated by qRT-PCR and fluorescence-activated
cell sorting (FACS). Expression of CD105 in primary HCC was evaluated by immunohistochemistry (IHC) or immunofluorescence (IF). The relation between CD105 expression status and HCC prognosis was analyzed using microarray data of 244 HCC cases HSP inhibitor and by Kaplan-Meier survival analysis. [Results] 5-FU or epirubicin treatment resulted in the generation of CD90+ and CD1 05+ cells in vitro in Huh1 and Huh7 cells originally containing no CD90+ or CD105+ cells, with enrichment of EpCAM+ cells. IF analysis validated the de novo generation of CD1 05+ cells medchemexpress with activation of ENG encoding CD105 and epithelial-mesenchymal transition (EMT) program regulators SNAI1 and SNAI2 evaluated by qRT-PCR analysis. IHC
analysis indicated that CD105+ cells were morphologically identical to the vascular endothelial cells in untreated primary HCCs. However, surgically resected specimens after transcatheter arterial chemoembolization (TACE) clearly indicated that the CD1 05+ cancer cells survived at the periphery of the tumor. Kaplan-Meier survival analysis indicated that HCCs abundantly expressing ENG showed poor prognosis after surgery with statistical significance (P = 0.02). [Conclusions] Vascular endothelial marker CD105 is not only expressed in CD90+ mesenchymal cancer cells but is also activated after chemotherapy and TACE in EpCAM+ epithelial cancer cells accompanied by the activation of EMT regulators SNAI1 and SNAI2. CD105 may be good marker for the evaluation of EMT and could be useful for evaluating prognosis in HCC patients who receive surgery. Disclosures: Mariko Yoshida – Grant/Research Support: Bayer Shuichi Kaneko – Grant/Research Support: MDS, Co., Inc, Chugai Pharma., Co.