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 language | English |
|---|---|
| Pages (from-to) | 157-164 |
| Number of pages | 8 |
| Journal | Cancer Science |
| Volume | 104 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2013 Feb |
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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 journal › Article
}
TY - JOUR
T1 - Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells
AU - Kabashima-Niibe, Ayano
AU - Higuchi, Hajime
AU - Takaishi, Hiromasa
AU - Masugi, Yohei
AU - Matsuzaki, Yumi
AU - Mabuchi, Yo
AU - Funakoshi, Shinsuke
AU - Adachi, Masayuki
AU - Hamamoto, Yasuo
AU - Kawachi, Shigeyuki
AU - Aiura, Koichi
AU - Kitagawa, Yuukou
AU - Sakamoto, Michiie
AU - Hibi, Toshifumi
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84873702799&partnerID=8YFLogxK
U2 - 10.1111/cas.12059
DO - 10.1111/cas.12059
M3 - Article
C2 - 23121112
AN - SCOPUS:84873702799
VL - 104
SP - 157
EP - 164
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 2
ER -