Establishment of an Immunocompetent Metastasis Rat Model with Hepatocyte Cancer Stem Cells

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题名:	Establishment of an Immunocompetent Metastasis Rat Model with Hepatocyte Cancer Stem Cells
作者:	Wu, S (Wu, Semon) Tseng, IC (Tseng, I-Chieh) Huang, WC (Huang, Wen-Cheng) Su, CW (Su, Cheng-Wen) Lai, YH (Lai, Yu-Heng) Lin, C (Lin, Che) Lee, AYL (Lee, Alan Yueh-Luen) Kuo, CY (Kuo, Chan-Yen) Su, LY (Su, Li-Yu) Lee, MC (Lee, Ming-Cheng) Hsu, TC (Hsu, Te-Cheng) Yu, CH (Yu, Chun-Hsien)
贡献者:	生科系
关键词:	hepatocyte cancer stem cell cell renew drug resistance metastasis xenografts
日期:	2020-12
上传时间:	2021-01-19 09:53:31 (UTC+8)
摘要:	Simple Summary Cancer stem cells (CSCs) are considered responsible for the maintenance, metastasis, and recurrence of various tumors. Here, we isolated a novel CSCs, TW-1, which can self-renew, differentiate and resistant to sorafenib. We also established novel orthotopic and metastasis models in immunocompetent rats with TW-1. These immunocompetent animal model can provide a normal physiological condition for anti-cancer drug screening. Using machine learning, we predicted HCC (AUCs > 0.9) with eight biomarkers including 6 highly expressed in TW-1/HTC and 2 well-known biomarkers from recent HCC studies. In conclusion, our results showed that TW-1 was a novel rat CSC line, and the animal model established with TW-1, is not only useful for the study of metastasis of HCC but also preclinical cancer drug screening. Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. Cancer stem cells (CSCs) are responsible for the maintenance, metastasis, and relapse of various tumors. The effects of CSCs on the tumorigenesis of HCC are still not fully understood, however. We have recently established two new rat HCC cell lines HTC and TW-1, which we isolated from diethylnitrosamine-induced rat liver cancer. Results showed that TW-1 expressed the genetic markers of CSCs, including CD133, GSTP1, CD44, CD90, and EpCAM. Moreover, TW-1 showed higher tolerance to sorafenib than HTC did. In addition, tumorigenesis and metastasis were observed in nude mice and wild-type rats with TW-1 xenografts. Finally, we combined highly expressed genes in TW-1/HTC with well-known biomarkers from recent HCC studies to predict HCC-related biomarkers and able to identify HCC with AUCs > 0.9 after machine learning. These results indicated that TW-1 was a novel rat CSC line, and the mice or rat models we established with TW-1 has great potential on HCC studies in the future.
關聯:	CANCERS 卷冊: 12 期: 12 文獻號碼: 3721
显示于类别:	[生命科學系] 期刊論文

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