A stem cell medium containing neural stimulating factor induces a pancreatic cancer stem-like cell-enriched population

Yusaku Watanabe, Kiyoshi Yoshimura, Koichi Yoshikawa, Ryoichi Tsunedomi, Yoshitaro Shindo, Sou Matsukuma, Noriko Maeda, Shinsuke Kanekiyo, Nobuaki Suzuki, Atsuo Kuramasu, Kouhei Sonoda, Koji Tamada, Sei Kobayashi, Hideyuki Saya, Shoichi Hazama, Masaki Oka

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cancer stem cells (CSCs) have been studied for their self-renewal capacity and pluripotency, as well as their resistance to anticancer therapy and their ability to metastasize to distant organs. CSCs are difficult to study because their population is quite low in tumor specimens. To overcome this problem, we established a culture method to induce a pancreatic cancer stem-like cell (P-CSLC)-enriched population from human pancreatic cancer cell lines. Human pancreatic cancer cell lines established at our department were cultured in CSC-inducing media containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), neural cell survivor factor-1 (NSF-1), and N-acetylcysteine. Sphere cells were obtained and then transferred to a laminin-coated dish and cultured for approximately two months. The surface markers, gene expression, aldehyde dehydrogenase (ALDH) activity, cell cycle, and tumorigenicity of these induced cells were examined for their stem cell-like characteristics. The population of these induced cells expanded within a few months. The ratio of CD24high, CD44high, epithelial specific antigen (ESA) high, and CD44variant (CD44v) high cells in the induced cells was greatly enriched. The induced cells stayed in the G0/G1 phase and demonstrated mesenchymal and stemness properties. The induced cells had high tumorigenic potential. Thus, we established a culture method to induce a P-CSLCenriched population from human pancreatic cancer cell lines. The CSLC population was enriched approximately 100-fold with this method. Our culture method may contribute to the precise analysis of CSCs and thus support the establishment of CSC-targeting therapy.

Original languageEnglish
Pages (from-to)1857-1866
Number of pages10
JournalInternational journal of oncology
Volume45
Issue number5
DOIs
Publication statusPublished - 2014 Nov 1

Keywords

  • Cancer stem cells
  • Cell culture method
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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