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

被引:749
作者
DeRose, Yoko S. [1 ]
Wang, Guoying [1 ]
Lin, Yi-Chun [1 ]
Bernard, Philip S. [2 ,3 ]
Buys, Saundra S. [4 ]
Ebbert, Mark T. W. [3 ]
Factor, Rachel [2 ]
Matsen, Cindy [5 ]
Milash, Brett A. [6 ]
Nelson, Edward [5 ]
Neumayer, Leigh [5 ]
Randall, R. Lor [7 ]
Stijleman, Inge J. [2 ]
Welm, Bryan E. [1 ,5 ]
Welm, Alana L. [1 ]
机构
[1] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA
[2] Univ Utah, Dept Pathol, Huntsman Canc Inst, Salt Lake City, UT USA
[3] Associated Reg & Univ Pathologists Inst Clin & Ex, Salt Lake City, UT USA
[4] Univ Utah, Dept Internal Med, Div Med Oncol, Huntsman Canc Inst, Salt Lake City, UT 84112 USA
[5] Univ Utah, Dept Surg, Huntsman Canc Inst, Salt Lake City, UT USA
[6] Univ Utah, Hlth Sci Ctr, Bioinformat Core Facil, Huntsman Canc Inst, Salt Lake City, UT USA
[7] Univ Utah, Dept Orthopaed Surg, Huntsman Canc Inst, Salt Lake City, UT USA
关键词
MESENCHYMAL STEM-CELLS; MOUSE MODELS; IN-VITRO; MICE; XENOGRAFTS; SUBTYPES; PREDICTOR; LINES;
D O I
10.1038/nm.2454
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1514 / U227
页数:8
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