Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived extracellular vesicles

Ting Yan, Akifumi Mizutani, Ling Chen, Mai Takaki, Yuki Hiramoto, Shuichi Matsuda, Tsukasa Shigehiro, Tomonari Kasai, Takayuki Kudoh, Hiroshi Murakami, Junko Masuda, Mary J.C. Hendrix, Luigi Strizzi, David S. Salomon, Li Fu, Masaharu Seno

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Several studies have shown that cancer niche can perform an active role in the regulation of tumor cell maintenance and progression through extracellular vesicles-based intercellular communication. However, it has not been reported whether this vesicle-mediated communication affects the malignant transformation of normal stem cells/progenitors. We have previously reported that the conditioned medium derived from the mouse Lewis Lung Carcinoma (LLC) cell line can convert mouse induced pluripotent stem cells (miPSCs) into cancer stem cells (CSCs), indicating that normal stem cells when placed in an aberrant microenvironment can give rise to functionally active CSCs. Here, we focused on the contribution of tumor-derived extracellular vesicles (tEVs) that are secreted from LLC cells to induce the transformation of miPSCs into CSCs. We isolated tEVs from the conditioned medium of LLC cells, and then the differentiating miPSCs were exposed to tEVs for 4 weeks. The resultant tEV treated cells (miPS-LLCev) expressed Nanog and Oct3/4 proteins comparable to miPSCs. The frequency of sphere formation of the miPS-LLCev cells in suspension culture indicated that the self-renewal capacity of the miPS-LLCev cells was significant. When the miPS-LLCev cells were subcutaneously transplanted into Balb/c nude mice, malignant liposarcomas with extensive angiogenesis developed. miPS-LLCevPT and miPS-LLCevDT, the cells established from primary site and disseminated liposarcomas, respectively, showed their capacities to self-renew and differentiate into adipocytes and endothelial cells. Moreover, we confirmed the secondary liposarcoma development when these cells were transplanted. Taken together, these results indicate that miPS-LLCev cells possess CSC properties. Thus, our current study provides the first evidence that tEVs have the potential to induce CSC properties in normal tissue stem cells/progenitors.

Original languageEnglish
Pages (from-to)572-584
Number of pages13
JournalJournal of Cancer
Volume5
Issue number7
DOIs
Publication statusPublished - 2014

Keywords

  • Cancer stem cells
  • Cancerous niche
  • Extracellular vesicles
  • Liposarcoma
  • Mouse induced pluripotent stem cells

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived extracellular vesicles'. Together they form a unique fingerprint.

  • Cite this

    Yan, T., Mizutani, A., Chen, L., Takaki, M., Hiramoto, Y., Matsuda, S., Shigehiro, T., Kasai, T., Kudoh, T., Murakami, H., Masuda, J., Hendrix, M. J. C., Strizzi, L., Salomon, D. S., Fu, L., & Seno, M. (2014). Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived extracellular vesicles. Journal of Cancer, 5(7), 572-584. https://doi.org/10.7150/jca.8865