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אסיף מאגר המחקר החקלאי
פותח על ידי קלירמאש פתרונות בע"מ -
Involvement of host stroma cells and tissue fibrosis in pancreatic tumor development in transgenic mice
Year:
2012
Source of publication :
PLoS ONE
Authors :
גנין, אולגה
;
.
לביא, עדי
;
.
ספקטור, איתי
;
.
פינס, מרק
;
.
Volume :
7
Co-Authors:
Spector, I., Institute of Animal Sciences, The Volcani Center, Bet Dagan, Israel, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot, Israel
Zilberstein, Y., The Sackler Cellular and Molecular Imaging Center (SCMIC), Tel Aviv University, Tel Aviv, Israel
Lavy, A., Institute of Animal Sciences, The Volcani Center, Bet Dagan, Israel, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot, Israel
Nagler, A., Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel
Genin, O., Institute of Animal Sciences, The Volcani Center, Bet Dagan, Israel
Pines, M., Institute of Animal Sciences, The Volcani Center, Bet Dagan, Israel
Facilitators :
From page:
0
To page:
0
(
Total pages:
1
)
Abstract:
Introduction: Stroma cells and extracellular matrix (ECM) components provide the pivotal microenvironment for tumor development. The study aimed to evaluate the importance of the pancreatic stroma for tumor development. Methods: Pancreatic tumor cells were implanted subcutaneously into green fluorescent protein transgenic mice, and stroma cells invading the tumors were identified through immunohistochemistry. Inhibition of tumor invasion by stroma cells was achieved with halofuginone, an inhibitor of TGFβ/Smad3 signaling, alone or in combination with chemotherapy. The origin of tumor ECM was evaluated with species-specific collagen I antibodies and in situ hybridization of collagen α1(I) gene. Pancreatic fibrosis was induced by cerulean injection and tumors by spleen injection of pancreatic tumor cells. Results: Inhibition of stroma cell infiltration and reduction of tumor ECM levels by halofuginone inhibited development of tumors derived from mouse and human pancreatic cancer cells. Halofuginone reduced the number only of stroma myofibroblasts expressing both contractile and collagen biosynthesis markers. Both stroma myofibroblasts and tumor cells generated ECM that contributes to tumor growth. Combination of treatments that inhibit stroma cell infiltration, cause apoptosis of myofibroblasts and inhibit Smad3 phosphorylation, with chemotherapy that increases tumor-cell apoptosis without affecting Smad3 phosphorylation was more efficacious than either treatment alone. More tumors developed in fibrotic than in normal pancreas, and prevention of tissue fibrosis greatly reduced tumor development. Conclusions: The utmost importance of tissue fibrosis and of stroma cells for tumor development presents potential new therapy targets, suggesting combination therapy against stroma and neoplastic cells as a treatment of choice. © 2012 Spector et al.
Note:
Related Files :
Animals
apoptosis
Carcinogenesis
gene expression
Male
mice
עוד תגיות
תוכן קשור
More details
DOI :
10.1371/journal.pone.0041833
Article number:
0
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
20848
Last updated date:
02/03/2022 17:27
Creation date:
16/04/2018 23:39
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Scientific Publication
Involvement of host stroma cells and tissue fibrosis in pancreatic tumor development in transgenic mice
7
Spector, I., Institute of Animal Sciences, The Volcani Center, Bet Dagan, Israel, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot, Israel
Zilberstein, Y., The Sackler Cellular and Molecular Imaging Center (SCMIC), Tel Aviv University, Tel Aviv, Israel
Lavy, A., Institute of Animal Sciences, The Volcani Center, Bet Dagan, Israel, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot, Israel
Nagler, A., Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel
Genin, O., Institute of Animal Sciences, The Volcani Center, Bet Dagan, Israel
Pines, M., Institute of Animal Sciences, The Volcani Center, Bet Dagan, Israel
Involvement of host stroma cells and tissue fibrosis in pancreatic tumor development in transgenic mice
Introduction: Stroma cells and extracellular matrix (ECM) components provide the pivotal microenvironment for tumor development. The study aimed to evaluate the importance of the pancreatic stroma for tumor development. Methods: Pancreatic tumor cells were implanted subcutaneously into green fluorescent protein transgenic mice, and stroma cells invading the tumors were identified through immunohistochemistry. Inhibition of tumor invasion by stroma cells was achieved with halofuginone, an inhibitor of TGFβ/Smad3 signaling, alone or in combination with chemotherapy. The origin of tumor ECM was evaluated with species-specific collagen I antibodies and in situ hybridization of collagen α1(I) gene. Pancreatic fibrosis was induced by cerulean injection and tumors by spleen injection of pancreatic tumor cells. Results: Inhibition of stroma cell infiltration and reduction of tumor ECM levels by halofuginone inhibited development of tumors derived from mouse and human pancreatic cancer cells. Halofuginone reduced the number only of stroma myofibroblasts expressing both contractile and collagen biosynthesis markers. Both stroma myofibroblasts and tumor cells generated ECM that contributes to tumor growth. Combination of treatments that inhibit stroma cell infiltration, cause apoptosis of myofibroblasts and inhibit Smad3 phosphorylation, with chemotherapy that increases tumor-cell apoptosis without affecting Smad3 phosphorylation was more efficacious than either treatment alone. More tumors developed in fibrotic than in normal pancreas, and prevention of tissue fibrosis greatly reduced tumor development. Conclusions: The utmost importance of tissue fibrosis and of stroma cells for tumor development presents potential new therapy targets, suggesting combination therapy against stroma and neoplastic cells as a treatment of choice. © 2012 Spector et al.
Scientific Publication
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