TY - JOUR
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 B.
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.
AB - 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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U2 - 10.1158/0008-5472.CAN-12-4081
DO - 10.1158/0008-5472.CAN-12-4081
M3 - Article
C2 - 23737486
AN - SCOPUS:84881415504
SN - 0008-5472
VL - 73
SP - 4885
EP - 4897
JO - Cancer research
JF - Cancer research
IS - 15
ER -