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

Semon Wu,Cheng-Wen Su,Chan-Yen Kuo,Chun-Hsien Yu,Alan Yueh-Luen Lee,Che Lin,Ming-Cheng Lee,Li-Yu Su,Te-Cheng Hsu,Wen-Cheng Huang,I-Chieh Tseng,Yu-Heng Lai

doi:10.3390/cancers12123721

Abstract

Simple SummaryCancer 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.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common cancers and is the leading cause of cancer mortality in many countries, including Taiwan [1]
These results suggested that sorafenib induced sorafenib-treated TW-1 (Figure 4B)
TW-1 expressed various markers that are unique in stem cell, such as CD133, GSTP1, CD44, and epithelial cell adhesion molecule (EpCAM), expressed various markers that are unique in stem cell, such as CD133, GSTP1, CD44, and EpCAM, which was identified as a cancer cell line with progenitor or stem cell-like properties

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common cancers and is the leading cause of cancer mortality in many countries, including Taiwan [1]. With the understanding of solid cancers, cancer stem cells (CSCs) have become a key topic of research interest. CSCs share similar cell surface markers including CD44, CD24, CD133, CD166, and epithelial cell adhesion molecule (EpCAM) [4,6,7,8,9,10,11], and self-renew, differentiate into different lineages, and utilize common signaling pathways, which happened in general pluripotent stem cells [12,13,14,15]. The significant difference between these two types of stem cells are the ability to form malignant tumors when transplanted into animals [15]. CSCs-derived tumors are resistant to chemotherapeutic agents and prone to recurrence and distant metastases

Methods

Results

Conclusion