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PMID: 17415413 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression.

The Journal of clinical investigation ·Vol. 117 ·No. 5 ·2007-05-00 ·Pages 1305-13

Biswas S, Guix M, Rinehart C, Dugger TC, Chytil A, Moses HL, Freeman ML, Arteaga CL

Abstract

We investigated whether TGF-beta induced by anticancer therapies accelerates tumor progression. Using the MMTV/PyVmT transgenic model of metastatic breast cancer, we show that administration of ionizing radiation or doxorubicin caused increased circulating levels of TGF-beta1 as well as increased circulating tumor cells and lung metastases. These effects were abrogated by administration of a neutralizing pan-TGF-beta antibody. Circulating polyomavirus middle T antigen-expressing tumor cells did not grow ex vivo in the presence of the TGF-beta antibody, suggesting autocrine TGF-beta is a survival signal in these cells. Radiation failed to enhance lung metastases in mice bearing tumors that lack the type II TGF-beta receptor, suggesting that the increase in metastases was due, at least in part, to a direct effect of TGF-beta on the cancer cells. These data implicate TGF-beta induced by anticancer therapy as a pro-metastatic signal in tumor cells and provide a rationale for the simultaneous use of these therapies in combination with TGF-beta inhibitors.

MeSH Terms
Animals Antibodies, Blocking/therapeutic use Antigens, Polyomavirus Transforming/physiology Cell Line, Tumor Female Humans Lung Neoplasms/immunology,prevention & control,secondary Mammary Neoplasms, Experimental/immunology,therapy Mammary Tumor Virus, Mouse/physiology Mice Mice, Transgenic Neoplasms, Radiation-Induced/immunology,pathology,prevention & control Neoplastic Cells, Circulating/immunology,pathology Retroviridae Infections/pathology,prevention & control Signal Transduction/physiology Transforming Growth Factor beta/antagonists & inhibitors,immunology Tumor Virus Infections/pathology,prevention & control
Chemicals
Antibodies, Blocking Antigens, Polyomavirus Transforming Transforming Growth Factor beta
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Biswas Swati
Department of Cancer Biology, Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2220 Pierce Avenue, Nashville, TN 37232, USA.
Guix Marta
Rinehart Cammie
Dugger Teresa C
Chytil Anna
Moses Harold L
Freeman Michael L
Arteaga Carlos L
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI30740
Published
2007-05-00
Epub
2007-00-05
Pages
1305-13
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1838926
Subset
IM
Grants
NCI NIH HHS · R01 CA062212 · United States
NCI NIH HHS · R01 CA 62212 · United States
NCI NIH HHS · R01 CA 102162 · United States
NCI NIH HHS · P50 CA098131 · United States
NCI NIH HHS · R01 CA102162 · United States
NCI NIH HHS · P30 CA 68485 · United States
NCI NIH HHS · P30 CA068485 · United States
NCI NIH HHS · R01 CA 38079 · United States
NCI NIH HHS · P50 CA 98131 · United States
NCI NIH HHS · R01 CA 85492 · United States
NCI NIH HHS · R01 CA038079 · United States
NCI NIH HHS · R01 CA085492 · United States
Corrections
ErratumIn
PMID: 28248204
External Links
PubMed source DOI: 10.1172/JCI30740 PMC Full Text View journal details
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