A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models

Xiaomei Zhang, Sofie Claerhout, Aleix Prat, Lacey E. Dobrolecki, Ivana Petrovic, Qing Lai, Melissa D. Landis, Lisa Wiechmann, Rachel Schiff, Mario Giuliano, Helen Wong, Suzanne W. Fuqua, Alejandro Contreras, Carolina Gutierrez, Jian Huang, Sufeng Mao, Anne C. Pavlick, Amber M. Froehlich, Meng Fen Wu, Anna TsimelzonSusan G. Hilsenbeck, Edward S. Chen, Pavel Zuloaga, Chad A. Shaw, Mothaffar F. Rimawi, Charles M. Perou, Gordon Mills, Jenny C. Chang, Michael T. Lewis

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort of human breast tumors grown in the epithelium-freemammary fat pad of severe combined immunodeficient (SCID)/Beige and nonobese diabetic (NOD)/SCID/IL-2g-receptor null (NSG) mice under a series of transplant conditions. Both models yielded stably transplantable xenografts at comparably high rates (∼21% and ∼19%, respectively).Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 32 stably transplantable xenograft lines were established, representing 25 unique patients. Most tumors yielding xenografts were "triple-negative" [estrogen receptor (ER)-progesterone receptor (PR)-HER2+; n = 19]. However, we established lines from 3 ER-PR-HER2+ tumors, one ER+PR-HER2-, oneER+PR+HER2-, and one "triple-positive" (ER+PR+HER2+) tumor. Serially passaged xenografts show biologic consistency with the tumor of origin, are phenotypically stable across multiple transplant generations at the histologic, transcriptomic, proteomic, and genomic levels, and show comparable treatment responses as those observed clinically. Xenografts representing 12 patients, including 2 ER+ lines, showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource for preclinical studies investigating treatment response and metastasis.

Original languageEnglish (US)
Pages (from-to)4885-4897
Number of pages13
JournalCancer Research
Volume73
Issue number15
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

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Heterografts
Progesterone Receptors
Estrogen Receptors
Breast Neoplasms
Neoplasms
Neoplasm Metastasis
Transplants
Proteomics
Adipose Tissue
Estradiol
Breast
Epithelium
Lung
Therapeutics
Research

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models. / Zhang, Xiaomei; Claerhout, Sofie; Prat, Aleix; Dobrolecki, Lacey E.; Petrovic, Ivana; Lai, Qing; Landis, Melissa D.; Wiechmann, Lisa; Schiff, Rachel; Giuliano, Mario; Wong, Helen; Fuqua, Suzanne W.; Contreras, Alejandro; Gutierrez, Carolina; Huang, Jian; Mao, Sufeng; Pavlick, Anne C.; Froehlich, Amber M.; Wu, Meng Fen; Tsimelzon, Anna; Hilsenbeck, Susan G.; Chen, Edward S.; Zuloaga, Pavel; Shaw, Chad A.; Rimawi, Mothaffar F.; Perou, Charles M.; Mills, Gordon; Chang, Jenny C.; Lewis, Michael T.

In: Cancer Research, Vol. 73, No. 15, 01.08.2013, p. 4885-4897.

Research output: Contribution to journalArticle

Zhang, X, Claerhout, S, Prat, A, Dobrolecki, LE, Petrovic, I, Lai, Q, Landis, MD, Wiechmann, L, Schiff, R, Giuliano, M, Wong, H, Fuqua, SW, Contreras, A, Gutierrez, C, Huang, J, Mao, S, Pavlick, AC, Froehlich, AM, Wu, MF, Tsimelzon, A, Hilsenbeck, SG, Chen, ES, Zuloaga, P, Shaw, CA, Rimawi, MF, Perou, CM, Mills, G, Chang, JC & Lewis, MT 2013, 'A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models', Cancer Research, vol. 73, no. 15, pp. 4885-4897. https://doi.org/10.1158/0008-5472.CAN-12-4081
Zhang, Xiaomei ; Claerhout, Sofie ; Prat, Aleix ; Dobrolecki, Lacey E. ; Petrovic, Ivana ; Lai, Qing ; Landis, Melissa D. ; Wiechmann, Lisa ; Schiff, Rachel ; Giuliano, Mario ; Wong, Helen ; Fuqua, Suzanne W. ; Contreras, Alejandro ; Gutierrez, Carolina ; Huang, Jian ; Mao, Sufeng ; Pavlick, Anne C. ; Froehlich, Amber M. ; Wu, Meng Fen ; Tsimelzon, Anna ; Hilsenbeck, Susan G. ; Chen, Edward S. ; Zuloaga, Pavel ; Shaw, Chad A. ; Rimawi, Mothaffar F. ; Perou, Charles M. ; Mills, Gordon ; Chang, Jenny C. ; Lewis, Michael T. / A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models. In: Cancer Research. 2013 ; Vol. 73, No. 15. pp. 4885-4897.
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T1 - A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models

AU - Zhang, Xiaomei

AU - Claerhout, Sofie

AU - Prat, Aleix

AU - Dobrolecki, Lacey E.

AU - Petrovic, Ivana

AU - Lai, Qing

AU - Landis, Melissa D.

AU - Wiechmann, Lisa

AU - Schiff, Rachel

AU - Giuliano, Mario

AU - Wong, Helen

AU - Fuqua, Suzanne W.

AU - Contreras, Alejandro

AU - Gutierrez, Carolina

AU - Huang, Jian

AU - Mao, Sufeng

AU - Pavlick, Anne C.

AU - Froehlich, Amber M.

AU - Wu, Meng Fen

AU - Tsimelzon, Anna

AU - Hilsenbeck, Susan G.

AU - Chen, Edward S.

AU - Zuloaga, Pavel

AU - Shaw, Chad A.

AU - Rimawi, Mothaffar F.

AU - Perou, Charles M.

AU - Mills, Gordon

AU - Chang, Jenny C.

AU - Lewis, Michael T.

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort of human breast tumors grown in the epithelium-freemammary fat pad of severe combined immunodeficient (SCID)/Beige and nonobese diabetic (NOD)/SCID/IL-2g-receptor null (NSG) mice under a series of transplant conditions. Both models yielded stably transplantable xenografts at comparably high rates (∼21% and ∼19%, respectively).Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 32 stably transplantable xenograft lines were established, representing 25 unique patients. Most tumors yielding xenografts were "triple-negative" [estrogen receptor (ER)-progesterone receptor (PR)-HER2+; n = 19]. However, we established lines from 3 ER-PR-HER2+ tumors, one ER+PR-HER2-, oneER+PR+HER2-, and one "triple-positive" (ER+PR+HER2+) tumor. Serially passaged xenografts show biologic consistency with the tumor of origin, are phenotypically stable across multiple transplant generations at the histologic, transcriptomic, proteomic, and genomic levels, and show comparable treatment responses as those observed clinically. Xenografts representing 12 patients, including 2 ER+ lines, showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource for preclinical studies investigating treatment response and metastasis.

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