Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 169, Issue 2, Pages 381-390Publisher
SPRINGER
DOI: 10.1007/s10549-018-4685-2
Keywords
Triple-negative breast cancer; Claudin-low; Patient-derived xenograft; Mesenchymal; Extracellular matrix; Decellularized tumor scaffold; Collagen
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Funding
- National Institute of Health (NIH) [R01-CA125806, R01-CA174785]
- Biospecimen Core Laboratory of the Louisiana Cancer Research Consortium
- National Institute of General Medical Sciences of the National Institutes of Health [U54 GM104940]
- Krewe de Pink
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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 developing 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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