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Poster display session

173P - Cancer stem-like phenotypes including immune surveillance and its responsible genes in induced liver cancer stem-like cells


23 Nov 2019


Poster display session


Tumour Site

Hepatobiliary Cancers


Ryouichi Tsunedomi


Annals of Oncology (2019) 30 (suppl_9): ix42-ix67. 10.1093/annonc/mdz422


R. Tsunedomi1, K. Yoshimura2, Y. Kimura1, M. Nishiyama1, S. Matsukuma1, Y. Tokumitsu1, S. Tomochika1, M. Iida1, N. Suzuki1, S. Takeda1, S. Yoshino3, S. Hazama4, H. Nagano1

Author affiliations

  • 1 Department Of Gastroenterological, Breast And Endocrine Surgery, Yamaguchi University Graduate School of Medicine, 755-0046 - Ube/JP
  • 2 Clinical Research Institute For Clinical Pharmacology And Therapeutics, Showa University, Shinagawa/JP
  • 3 Oncology Center, Yamaguchi University Hospital, Ube/JP
  • 4 Department Of Translational Research And Developmental Therapeutics Against Cancer, Yamaguchi University, Ube/JP


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Abstract 173P


Cancer stem cells are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) from hepatoma cell lines using a unique medium.


The human hepatoma cell line SK-HEP-1 was used as parental cells for CSLC induction. To assess the chemoresistance and liver metastasis, MTS assay and splenic injection were performed, respectively. RNA-seq analysis followed by gene set enrichment analysis (GSEA) was performed with cell line derivatives and clinical specimens of hepatoma. Protein expressions were conducted by western blotting, flow-cytometry, or ELISA. Knock-out experiments was accomplished by CRISPR-Cas9 genome-editing. Following rescue experiments were performed with an expression vector.


The obtained CSLCs showed increased metastatic potentials and resistance to anti-cancer drugs including molecularly targeted drugs for liver cancer. Regarding immune resistance, CSLCs showed increased proportion of positive cells for PD-L1 and PD-L2. In contrast to decreased membrane-bound MICA/MICB, increased soluble MICA in the medium were observed in CSLCs compared to those from the parental cells. As a result of integrated analysis with RNA-seq, a RAB3B was identified as an up-regulated gene in both CSLCs and poor prognostic liver cancers. Mono-allelic RAB3B knock-out cells showed altered sphere formation, significantly lower chemoresistance, and metastatic potential than that of parental cells, and those were rescued by the complementation of RAB3B. The knock-out cells also showed decreased PD-L1 and PD-L2 expressions in sphere induction medium than those in cells cultured with normal medium. GSEA following RNA-seq with the derivative cells revealed that negative enrichment of G2M checkpoint and positive enrichment of interferon response in CSLCs.


Our induced CSLCs showed characteristic phenotypes such as metastatic ability, chemo- and immune-resistances. The up-regulation of RAB3B may plays important roles in CSLCs.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study



Japan Society for the Promotion of Science.


All authors have declared no conflicts of interest.

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