Abstract
Background
Triple-negative breast cancer (TNBC) subtypes are clinically aggressive and cannot be treated with targeted therapeutics commonly used in other breast cancer subtypes. The claudin-low (CL) molecular subtype of TNBC has high rates of metastases, chemoresistance and recurrence. There exists an urgent need to identify novel therapeutic targets in TNBC; however, existing models utilized in target discovery research are limited. Patient-derived xenograft (PDX) models have emerged as superior models for target discovery experiments because they recapitulate features of patient tumors that are limited by cell-line derived xenograft methods.
Methods
We utilize immunohistochemistry, qRT-PCR and Western Blot to visualize tumor architecture, cellular composition, genomic and protein expressions of a new CL-TNBC PDX model (TU-BcX-2O0). We utilize tissue decellularization techniques to examine extracellular matrix composition of TU-BcX-2O0.
Results
Our laboratory successfully established a TNBC PDX tumor, TU-BCX-2O0, which represents a CL-TNBC subtype and maintains this phenotype throughout subsequent passaging. We dissected TU-BCx-2O0 to examine aspects of this complex tumor that can be targeted by develo** therapeutics, including the whole and intact breast tumor, specific cell populations within the tumor, and the extracellular matrix.
Conclusions
Here, we characterize a claudin-low TNBC patient-derived xenograft model that can be utilized for therapeutic research studies.
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Acknowledgements
This work was supported by grants from National Institute of Health (NIH) (Grant No. R01-CA125806 (MEB) and R01-CA174785 (BC-B). This work was also supported in part by the Biospecimen Core Laboratory of the Louisiana Cancer Research Consortium. We would especially like to acknowledge Alex Alfortish and Sharon Miller, who played integral roles in coordination and acquisition of TNBC tissue specimen. Additionally, this work was also supported in part by U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We are also appreciative of Krewe de Pink for their support in this project. Finally, we would also like to acknowledge the patients who consent to donate their tissue to benefit breast cancer research.
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Experiments performed in this study comply with current laws in the United States of America. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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Matossian, M.D., Burks, H.E., Bowles, A.C. et al. A novel patient-derived xenograft model for claudin-low triple-negative breast cancer. Breast Cancer Res Treat 169, 381–390 (2018). https://doi.org/10.1007/s10549-018-4685-2
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DOI: https://doi.org/10.1007/s10549-018-4685-2