A novel model of liver cancer stem cells developed from induced pluripotent stem cells

• Published in: British journal of cancer Vol. 122; no. 9; pp. 1378 - 1390
• Main Authors: Afify, Said M., Sanchez Calle, Anna, Hassan, Ghmkin, Kumon, Kazuki, Nawara, Hend M., Zahra, Maram H., Mansour, Hager M., Khayrani, Apriliana Cahya, Alam, Md Jahangir, Du, Juan, Seno, Akimasa, Iwasaki, Yoshiaki, Seno, Masaharu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2020; Nature Publishing Group
• Subjects: 631/67/70; 631/67/71; Animals; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinogenesis - drug effects; Carcinoma, Hepatocellular - etiology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Self Renewal - drug effects; Cell self-renewal; Culture Media, Conditioned - metabolism; Culture Media, Conditioned - pharmacology; Drug Resistance; Epidemiology; Hepatocellular carcinoma; Hepatocytes; Humans; Induced Pluripotent Stem Cells - drug effects; Induced Pluripotent Stem Cells - pathology; Liver - drug effects; Liver - pathology; Liver cancer; Liver Neoplasms - etiology; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Mice; Mice, Inbred BALB C; Molecular Medicine; Molecular modelling; Neoplastic Stem Cells - drug effects; Oncology; Pluripotency; Signal Transduction - drug effects; Stem cell transplantation; Stem cells; Tumorigenicity; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-020-0792-z

Background Liver cancer is the second most common cause of cancer-related death. Every type of tumours including liver cancer contains cancer stem cells (CSCs). To date, the molecular mechanism regulating the development of liver CSCs remains unknown. Methods In this study, we tried to generate a new model of liver CSCs by converting mouse induced pluripotent stem cells (miPSCs) with hepatocellular carcinoma (HCC) cell line Huh7 cells conditioned medium (CM). miPSCs treated with CM were injected into the liver of BALB/c nude mice. The developed tumours were then excised and analysed. Results The primary cultured cells from the malignant tumour possessed self-renewal capacity, differentiation potential and tumorigenicity in vivo, which were found rich in liver cancer-associated markers as well as CSC markers. Conclusions We established a model of liver CSCs converting from miPS and showed different stages of stemness during conversion process. Our CSC model will be important to assess the molecular mechanisms necessary to develop liver CSCs and could help in defeating liver cancer.