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, Yuukou Kitagawa, Michiie Sakamoto, Toshifumi Hibi

Research output: Contribution to journalArticle

71 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

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Epithelial-Mesenchymal Transition
Mesenchymal Stromal Cells
Pancreatic Neoplasms
Neoplastic Stem Cells
Myofibroblasts
Side-Population Cells
Neoplasms
Amyloid Precursor Protein Secretases
Cadherins
Heterografts
Small Interfering RNA
Smooth Muscle
Actins
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells. / Kabashima-Niibe, Ayano; Higuchi, Hajime; Takaishi, Hiromasa; Masugi, Yohei; Matsuzaki, Yumi; Mabuchi, Yo; Funakoshi, Shinsuke; Adachi, Masayuki; Hamamoto, Yasuo; Kawachi, Shigeyuki; Aiura, Koichi; Kitagawa, Yuukou; Sakamoto, Michiie; Hibi, Toshifumi.

In: Cancer Science, Vol. 104, No. 2, 02.2013, p. 157-164.

Research output: Contribution to journalArticle

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, vol. 104, no. 2, pp. 157-164. https://doi.org/10.1111/cas.12059
Kabashima-Niibe, Ayano ; Higuchi, Hajime ; Takaishi, Hiromasa ; Masugi, Yohei ; Matsuzaki, Yumi ; Mabuchi, Yo ; Funakoshi, Shinsuke ; Adachi, Masayuki ; Hamamoto, Yasuo ; Kawachi, Shigeyuki ; Aiura, Koichi ; Kitagawa, Yuukou ; Sakamoto, Michiie ; Hibi, Toshifumi. / Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells. In: Cancer Science. 2013 ; Vol. 104, No. 2. pp. 157-164.
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