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

Yoko S. Derose; Guoying Wang; Yi Chun Lin; Philip S. Bernard; Saundra S. Buys; Mark T.W. Ebbert; Rachel Factor; Cindy Matsen; Brett A. Milash; Edward Nelson; Leigh Neumayer; R. Lor Randall; Inge J. Stijleman; Bryan E. Welm; Alana L. Welm

doi:10.1038/nm.2454

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

Yoko S. Derose, Guoying Wang, Yi Chun Lin, Philip S. Bernard, Saundra S. Buys, Mark T.W. Ebbert, Rachel Factor, Cindy Matsen, Brett A. Milash, Edward Nelson, Leigh Neumayer, R. Lor Randall, Inge J. Stijleman, Bryan E. Welm, Alana L. Welm

Research output: Contribution to journal › Article › peer-review

785 Scopus citations

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.

Original language	English
Pages (from-to)	1514-1520
Number of pages	7
Journal	Nature Medicine
Volume	17
Issue number	11
DOIs	https://doi.org/10.1038/nm.2454
State	Published - Nov 2011

Bibliographical note

Funding Information:
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).

Funding

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).

Funders	Funder number
Department of Defense Breast Cancer Research Program	BC075015
American Association for Cancer Research
National Childhood Cancer Registry – National Cancer Institute	R01CA140296
National Childhood Cancer Registry – National Cancer Institute
Breast Cancer Research Foundation
Huntsman Cancer Foundation	P30 CA042014
Huntsman Cancer Foundation

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nm.2454

Cite this

Derose, Y. S., Wang, G., Lin, Y. C., Bernard, P. S., Buys, S. S., Ebbert, M. T. W., Factor, R., Matsen, C., Milash, B. A., Nelson, E., Neumayer, L., Randall, R. L., Stijleman, I. J., Welm, B. E., & Welm, A. L. (2011). Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nature Medicine, 17(11), 1514-1520. https://doi.org/10.1038/nm.2454

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

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.",

author = "Derose, {Yoko S.} and Guoying Wang and Lin, {Yi Chun} and Bernard, {Philip S.} and Buys, {Saundra S.} and Ebbert, {Mark T.W.} and Rachel Factor and Cindy Matsen and Milash, {Brett A.} and Edward Nelson and Leigh Neumayer and Randall, {R. Lor} and Stijleman, {Inge J.} and Welm, {Bryan E.} and Welm, {Alana L.}",

note = "Funding Information: 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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Derose, YS, Wang, G, Lin, YC, Bernard, PS, Buys, SS, Ebbert, MTW, Factor, R, Matsen, C, Milash, BA, Nelson, E, Neumayer, L, Randall, RL, Stijleman, IJ, Welm, BE & Welm, AL 2011, 'Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes', Nature Medicine, vol. 17, no. 11, pp. 1514-1520. https://doi.org/10.1038/nm.2454

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AU - Derose, Yoko S.

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AU - Stijleman, Inge J.

AU - Welm, Bryan E.

AU - Welm, Alana L.

N1 - Funding Information: 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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AB - 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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Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

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Cite this