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

Margarite D. Matossian, Hope E. Burks, Annie C. Bowles, Steven Elliott, Van T. Hoang, Rachel A. Sabol, Nicholas C. Pashos, Benjamen O’Donnell, Kristin S. Miller, Bahia M. Wahba, Bruce A. Bunnell, Krzysztof Moroz, Arnold H. Zea, Steven D. Jones, Augusto C. Ochoa, Amir A. Al-Khami, Fokhrul Hossain, Adam I. Riker, Lyndsay V. Rhodes, Elizabeth C. MartinLucio Miele, Matthew E. Burow, Bridgette M. Collins-Burow

Research output: Contribution to journalArticle

5 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)381-390
Number of pages10
JournalBreast Cancer Research and Treatment
Volume169
Issue number2
DOIs
StatePublished - 1 Jun 2018

Keywords

  • Claudin-low
  • Collagen
  • Decellularized tumor scaffold
  • Extracellular matrix
  • Mesenchymal
  • Patient-derived xenograft
  • Triple-negative breast cancer

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    Matossian, M. D., Burks, H. E., Bowles, A. C., Elliott, S., Hoang, V. T., Sabol, R. A., Pashos, N. C., O’Donnell, B., Miller, K. S., Wahba, B. M., Bunnell, B. A., Moroz, K., Zea, A. H., Jones, S. D., Ochoa, A. C., Al-Khami, A. A., Hossain, F., Riker, A. I., Rhodes, L. V., ... Collins-Burow, B. M. (2018). A novel patient-derived xenograft model for claudin-low triple-negative breast cancer. Breast Cancer Research and Treatment, 169(2), 381-390. https://doi.org/10.1007/s10549-018-4685-2