TGF-β blockade improves the distribution and efficacy of therapeutics in breast carcinoma by normalizing the tumor stroma

J Liu; S Liao; B Diop-Frimpong; W Chen; S Goel; K Naxerova; M Ancukiewicz; Y Boucher; RK Jain; L Xu

Journal article

TGF-β blockade improves the distribution and efficacy of therapeutics in breast carcinoma by normalizing the tumor stroma

J Liu, S Liao, B Diop-Frimpong, W Chen, S Goel, K Naxerova, M Ancukiewicz, Y Boucher, RK Jain, L Xu

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2012

DOI: 10.1073/pnas.1117610109

Abstract

Although the role of TGF-β in tumor progression has been studied extensively, its impact on drug delivery in tumors remains far from understood. In this study, we examined the effect of TGF-β blockade on the delivery and efficacy of conventional therapeutics and nanotherapeutics in orthotopic mammary carcinoma mouse models. We used both genetic (overexpression of sTβRII, a soluble TGF-βtype II receptor) and pharmacologic (1D11, a TGF-β neutralizing antibody) approaches to block TGF-β signaling. In two orthotopic mammary carcinoma models (human MDA-MB-231 and murine 4T1 cell lines), TGF-β blockade significantly decreased tumor growth and metastasis. TGF-β blockade also increased the recruitme..

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University of Melbourne Researchers

Shom Goel Author

Grants

Awarded by National Cancer Institute

Funding Acknowledgements

R.K.J. received research grants from Dyax, MedImmune, and Roche; received consultant fees from Dyax, Enlight, Noxxon, and SynDevRx; owns equity in Enlight, SynDevRx, and XTuit; and serves on the Board of Directors of XTuit and Board of Trustees of H&Q Healthcare Investors and H&Q Life Sciences Investors. Y.B. received consultant fees from XTuit. No reagents or funding from these companies were used in these studies. We thank Dannie Wang, Peigen Huang, and Carolyn Smith for their superb technical support; and Dr. Delphine Lacorre for her protocol for the doxorubicin distribution study. This work was supported in part by American Cancer Society Grant ACS122839-RSG-12-199-01 (to L.X.); National Institutes of Health Grants R01-CA85140 (to R.K.J.), R01-CA115767 (to R.K.J.), and R01-CA126642 (to R.K.J.); and a Department of Defense Breast Cancer Research Innovator Award W81XWH-10-1-0016 (to R.K.J.).