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Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes

Nature Medicine volume 17, pages 1514–1520 (2011)Cite this article

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Abstract

Development and preclinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically reproduce tumor growth and metastatic progression. We report new models for breast tumor growth and metastasis in the form of transplantable tumors derived directly from individuals undergoing treatment for breast cancer. These tumor grafts illustrate the diversity of human breast cancer and maintain essential features of the original tumors, including metastasis to specific sites. Co-engraftment of primary human mesenchymal stem cells maintains phenotypic stability of the grafts and increases tumor growth by promoting angiogenesis. We also report that tumor engraftment is a prognostic indicator of disease outcome for women with newly diagnosed breast cancer; orthotopic breast tumor grafting is a step toward individualized models for tumor growth, metastasis and prognosis. This bank of tumor grafts also serves as a publicly available resource for new models in which to study the biology of breast cancer.

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Figure 1: Tumor grafts resembled the original tumors from which they were derived.
Figure 2: Tumor grafts spontaneously metastasized to clinically relevant sites.
Figure 3: Co-engraftment of human mesenchymal stem cells (hMSCs) promotes vascularization and growth of tumor grafts.
Figure 4: Gene expression and copy number variations found in the original tumors are well maintained in tumor grafts.
Figure 5: Successful growth of primary tumor specimens as tumor grafts significantly predicted shortened survival times.

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Acknowledgements

We are grateful to the individuals who donated tissue toward this endeavor and the Associated Regional and University Pathologists Research Institute staff for performing the clinical stains. This work was supported by funding from the Department of Defense Breast Cancer Research Program (to A.L.W.; BC075015), the American Association for Cancer Research and Breast Cancer Research Foundation (to A.L.W.; 07−60−26−WELM) and the Huntsman Cancer Foundation. We also used the Huntsman Cancer Institute Tissue Resource and Application Core and Comparative Oncology Core facilities, which is supported in part by P30 CA042014 (to the Huntsman Cancer Institute).

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Authors and Affiliations

  1. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

    Yoko S DeRose, Guoying Wang, Yi-Chun Lin, Bryan E Welm & Alana L Welm

  2. Department of Pathology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

    Philip S Bernard, Rachel Factor & Inge J Stijleman

  3. The Associated Regional and University Pathologists Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, USA

    Philip S Bernard & Mark T W Ebbert

  4. Department of Internal Medicine, Medical Oncology Division, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

    Saundra S Buys

  5. Department of Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

    Cindy Matsen, Edward Nelson, Leigh Neumayer & Bryan E Welm

  6. Bioinformatics Core Facility, Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah, USA

    Brett A Milash

  7. Department of Orthopaedic Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

    R Lor Randall

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  1. Yoko S DeRose
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Contributions

Y.S.D., G.W., Y.-C.L., M.T.W.E., C.M. and I.J.S. performed the experiments. S.S.B., E.N., L.N. and R.L.R. provided tissues. Y.S.D., G.W., P.S.B., R.F., B.A.M., B.E.W. and A.L.W. analyzed the data. A.L.W. wrote the paper, and B.E.W. and P.S.B. edited the paper. A.L.W. supervised the project.

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Correspondence to Alana L Welm.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Results and Discussion, Supplementary Tables 2 and 3 and Supplementary Figures 1–32. (PDF 13517 kb)

Supplementary Table 1

Detailed patient, tumor and tumor graft information. (XLS 36 kb)

Supplementary Table 4

Expression data from preclustered intrinsic gene set. (TXT 2892 kb)

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DeRose, Y., Wang, G., Lin, YC. et al. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med 17, 1514–1520 (2011). https://doi.org/10.1038/nm.2454

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