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Inhibition of fibroblast to myofibroblast transition by halofuginone contributes to the chemotherapy-mediated antitumoral effect
Year:
2007
Source of publication :
Molecular Cancer Therapeutics
Authors :
Genina, Olga
;
.
Ilouze, Maya
;
.
Leon, Oded
;
.
Pines, Mark
;
.
Sheffer, Yuval
;
.
Volume :
6
Co-Authors:
Sheffer, Y., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Leon, O., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Pinthus, J.H., Department of Surgery, McMaster University, Hamilton, ON, Canada
Nagler, A., Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel
Mor, Y., Department of Urology, Chaim Sheba Medical Center, Tel Hashomer, Israel
Genin, O., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Iluz, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Kawada, N., Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
Yoshizato, K., Developmental Biology Laboratory, CLUSTER Project, Hiroshima University, Higashi-Hiroshima, Japan
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Facilitators :
From page:
570
To page:
577
(
Total pages:
8
)
Abstract:
Stromal myofibroblasts play an important role in tumor progression. The transition of fibroblasts to myofibroblasts is characterized by expression of smooth muscle genes and profuse synthesis of extracellular matrix proteins. We evaluated the efficacy of targeting fibroblast-to-myofibroblast transition with halofuginone on tumor progression in prostate cancer and Wilms' tumor xenografts. In both xenografts, low doses of halofuginone treatment, independent of the route of administration, resulted in a trend toward inhibition in tumor development. Moreover, halofuginone synergizes with low dose of docetaxel in prostate cancer and vincristine and dactinomycin in Wilms' tumor xenografts, resulting in significant reduction in tumor volume and weight comparable to the effect observed by high doses of the respective chemotherapies. In prostate cancer and Wilms' tumor xenografts, halofuginone, but not the respective chemotherapies, inhibited the synthesis of collagen type I, α-smooth muscle actin, transgelin, and cytoglobin, all of which are characteristics of activated myofibroblasts. Halofuginone, as the respective chemotherapies, increased the synthesis of Wilms' tumor suppressor gene product (WT-1) and prostate apoptosis response gene-4 (Par-4), resulting in apoptosis/necrosis. These results suggest that targeting the fibroblast-to-myofibroblast transition with halofuginone may synergize with low doses of chemotherapy in achieving a significant antitumoral effect, avoiding the need of high-dose chemotherapy and its toxicity without impairing treatment efficacy. Copyright © 2007 American Association for Cancer Research.
Note:
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More details
DOI :
10.1158/1535-7163.MCT-06-0468
Article number:
Affiliations:
Database:
Scopus
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
29656
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:48
Scientific Publication
Inhibition of fibroblast to myofibroblast transition by halofuginone contributes to the chemotherapy-mediated antitumoral effect
6
Sheffer, Y., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Leon, O., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Pinthus, J.H., Department of Surgery, McMaster University, Hamilton, ON, Canada
Nagler, A., Division of Hematology, Chaim Sheba Medical Center, Tel Hashomer, Israel
Mor, Y., Department of Urology, Chaim Sheba Medical Center, Tel Hashomer, Israel
Genin, O., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Iluz, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Kawada, N., Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
Yoshizato, K., Developmental Biology Laboratory, CLUSTER Project, Hiroshima University, Higashi-Hiroshima, Japan
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Inhibition of fibroblast to myofibroblast transition by halofuginone contributes to the chemotherapy-mediated antitumoral effect
Stromal myofibroblasts play an important role in tumor progression. The transition of fibroblasts to myofibroblasts is characterized by expression of smooth muscle genes and profuse synthesis of extracellular matrix proteins. We evaluated the efficacy of targeting fibroblast-to-myofibroblast transition with halofuginone on tumor progression in prostate cancer and Wilms' tumor xenografts. In both xenografts, low doses of halofuginone treatment, independent of the route of administration, resulted in a trend toward inhibition in tumor development. Moreover, halofuginone synergizes with low dose of docetaxel in prostate cancer and vincristine and dactinomycin in Wilms' tumor xenografts, resulting in significant reduction in tumor volume and weight comparable to the effect observed by high doses of the respective chemotherapies. In prostate cancer and Wilms' tumor xenografts, halofuginone, but not the respective chemotherapies, inhibited the synthesis of collagen type I, α-smooth muscle actin, transgelin, and cytoglobin, all of which are characteristics of activated myofibroblasts. Halofuginone, as the respective chemotherapies, increased the synthesis of Wilms' tumor suppressor gene product (WT-1) and prostate apoptosis response gene-4 (Par-4), resulting in apoptosis/necrosis. These results suggest that targeting the fibroblast-to-myofibroblast transition with halofuginone may synergize with low doses of chemotherapy in achieving a significant antitumoral effect, avoiding the need of high-dose chemotherapy and its toxicity without impairing treatment efficacy. Copyright © 2007 American Association for Cancer Research.
Scientific Publication
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