A novel patient-derived xenograft model for claudin-low triple-negative breast cancer

作者:Matossian Margarite D; Burks Hope E; Bowles Annie C; Elliott Steven; Hoang Van T; Sabol Rachel A; Pashos Nicholas C; O'Donnell Benjamen; Miller Kristin S; Wahba Bahia M; Bunnell Bruce A; Moroz Krzysztof; Zea Arnold H; Jones Steven D; Ochoa Augusto C; Al Khami Amir A; Hossain Fokhrul; Riker Adam I; Rhodes Lyndsay V; Martin Elizabeth C; Miele Lucio; Burow Matthew E; Collins Burow Bridgette M*
来源:Breast Cancer Research and Treatment, 2018, 169(2): 381-390.
DOI:10.1007/s10549-018-4685-2

摘要

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.

  • 出版日期2018-6