Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells

Ayano Kabashima-Niibe, Hajime Higuchi, Hiromasa Takaishi, Yohei Masugi, Yumi Matsuzaki, Yo Mabuchi, Shinsuke Funakoshi, Masayuki Adachi, Yasuo Hamamoto, Shigeyuki Kawachi, Koichi Aiura, Yuko Kitagawa, Michiie Sakamoto, Toshifumi Hibi

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Cancer-associated fibroblasts contribute to cancer progression that is caused by epithelial-mesenchymal transition (EMT). Recently, mesenchymal stem cells (MSCs) were found to be the major candidate involved in the development of tumor-promoting cancer stroma. Here we report that α-smooth muscle actin-positive myofibroblast-like cells originating from MSCs contribute to inducing EMT in side population cells of pancreatic cancer. More importantly, MSC-derived myofibroblasts function to maintain tumor-initiating stem cell-like characteristics, including augmenting expression levels of various stemness-associated genes, enhancing sphere- forming activity, promoting tumor formation in a mouse xenograft model, and showing resistance to anticancer drugs. Furthermore, both γ-secretase inhibitor and siRNA directed against Jagged-1 attenuated MSC-associated E-cadherin suppression and sphere formation in pancreatic cancer side population cells. Thus, our results suggest that MSC-derived myofibroblasts play important roles in regulating EMT and tumor-initiating stem cell-like properties of pancreatic cancer cells through an intermediating Notch signal.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalCancer science
Volume104
Issue number2
DOIs
Publication statusPublished - 2013 Feb

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Kabashima-Niibe, A., Higuchi, H., Takaishi, H., Masugi, Y., Matsuzaki, Y., Mabuchi, Y., Funakoshi, S., Adachi, M., Hamamoto, Y., Kawachi, S., Aiura, K., Kitagawa, Y., Sakamoto, M., & Hibi, T. (2013). Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells. Cancer science, 104(2), 157-164. https://doi.org/10.1111/cas.12059