TY - JOUR
T1 - Desmoplastic Reaction in 3D-Pancreatic Cancer Tissues Suppresses Molecular Permeability
AU - Matsusaki, Michiya
AU - Komeda, Misaki
AU - Mura, Simona
AU - Tanaka, Hiroyoshi Y.
AU - Kano, Mitsunobu R.
AU - Couvreur, Patrick
AU - Akashi, Mitsuru
N1 - Funding Information:
The authors are grateful to Ayami Hiura (Osaka University) for providing the histological sections. This work was supported by a Grant-in-Aid for Scientific Research (S) (232250040), (B) (26282138), a Grant-in-Aid for Scientific Research on Innovative Areas (26106717), and JST-PRESTO (10825). This work was also supported by Campus France PHC SAKURA 2016 (35990ZB).
Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/8/9
Y1 - 2017/8/9
N2 - The survival rate of pancreatic ductal adenocarcinoma is still the lowest among all types of cancers, primarily as a consequence of an important desmoplastic reaction. Although the presence of thick stromal tissues in pancreatic tumors has been reported, in vivo animal studies do not enable a clear understanding of the crosstalk between cancer cells and fibroblasts. Accordingly, this paper reports the design and characterization of an in vitro pancreatic cancer–stromal 3D-tissue model, which enhances the understanding of the interactions between cancer cells and fibroblasts and their influence on the secretion of extracellular matrix (ECM). 3D-tissue models comprising fibroblasts and pancreatic cancer cells (MiaPaCa-2 cell line) or colon cancer cells (HT29 cell line, used as a control) show decreased molecular permeability with increased cancer cell ratios. The 3D-MiaPaCa-2 tissues display an increase in the secretion of collagen as a function of the cancer cell ratio, whereas 3D-HT29 tissues do not show a significant difference. Notably, the secretion of ECM proteins from single fibroblasts in 3D-tissue models containing 90% MiaPaCa-2 cells is ten times higher than that under 10% cancer cell conditions. In vitro pancreatic cancer 3D-tissues will be a valuable tool to obtain information on the interactions between cancer and stromal cells.
AB - The survival rate of pancreatic ductal adenocarcinoma is still the lowest among all types of cancers, primarily as a consequence of an important desmoplastic reaction. Although the presence of thick stromal tissues in pancreatic tumors has been reported, in vivo animal studies do not enable a clear understanding of the crosstalk between cancer cells and fibroblasts. Accordingly, this paper reports the design and characterization of an in vitro pancreatic cancer–stromal 3D-tissue model, which enhances the understanding of the interactions between cancer cells and fibroblasts and their influence on the secretion of extracellular matrix (ECM). 3D-tissue models comprising fibroblasts and pancreatic cancer cells (MiaPaCa-2 cell line) or colon cancer cells (HT29 cell line, used as a control) show decreased molecular permeability with increased cancer cell ratios. The 3D-MiaPaCa-2 tissues display an increase in the secretion of collagen as a function of the cancer cell ratio, whereas 3D-HT29 tissues do not show a significant difference. Notably, the secretion of ECM proteins from single fibroblasts in 3D-tissue models containing 90% MiaPaCa-2 cells is ten times higher than that under 10% cancer cell conditions. In vitro pancreatic cancer 3D-tissues will be a valuable tool to obtain information on the interactions between cancer and stromal cells.
KW - extracellular matrix secretion
KW - pancreatic cancer
KW - permeability
KW - tissue engineering
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U2 - 10.1002/adhm.201700057
DO - 10.1002/adhm.201700057
M3 - Article
C2 - 28452178
AN - SCOPUS:85018964437
SN - 2192-2640
VL - 6
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 15
M1 - 1700057
ER -
