Open AccessMesenchymal stem cells regulate epithelial–mesenchymal transition and tumor progression of pancreatic cancer cells
Author(s) -
KabashimaNiibe Ayano,
Higuchi Hajime,
Takaishi Hiromasa,
Masugi Yohei,
Matsuzaki Yumi,
Mabuchi Yo,
Funakoshi Shinsuke,
Adachi Masayuki,
Hamamoto Yasuo,
Kawachi Shigeyuki,
Aiura Koichi,
Kitagawa Yuko,
Sakamoto Michiie,
Hibi Toshifumi
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12059
Subject(s) - mesenchymal stem cell , pancreatic cancer , epithelial–mesenchymal transition , cancer stem cell , cancer research , myofibroblast , biology , cancer cell , population , cancer associated fibroblasts , cancer , tumor progression , stroma , stem cell , microbiology and biotechnology , pathology , tumor microenvironment , medicine , immunology , metastasis , tumor cells , fibrosis , immunohistochemistry , environmental health , genetics
Cancer‐associated fibroblasts contribute to cancer progression that is caused by epithelial–mesenchymal transition ( EMT ). Recently, mesenchymal stem cells ( MSC s) 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 MSC s 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 si RNA 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.