In‑depth characterization of a new patient‑derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types

• M. D. Matossian ^[1] ; T. Chang ^[1] ; M. K. Wright ^[1] ; H. E. Burks ^[1] ; S. Elliott ^[1] ; R. A. Sabol ^[5] ; H. Wathieu ^[1] ; G. O. Windsor ^[1] ; M. S. Alzoubi ^[1] ; C. T. King ^[2] ; J. B. Bursavich ^[2] ; A. M. Ham ^[2] ; J. J. Savoie ^[2] ; K. Nguyen ^[1] ; M. Baddoo ^[1] ; E. Flemington ^[1] ; O. Sirenko ^[6] ; E. F. Cromwell ^[7] ; K. L. Hebert ^[1] ; F. Lau ^[8] ; R. Izadpanah ^[9] ; H. Brown ^[10] ; S. Sinha ^[10] ; J. Zabaleta ^[2] ; A. I. Riker ^[3] ; K. Moroz ^[11] ; L. Miele ^[2] ; A. H. Zea ^[12] ; A. Ochoa ^[2] ; B. A. Bunnell ^[4] ; B. M. Collins-Burow ^[1] ; E. C. Martin ^[2] ; M. E. Burow ^[1]
  1. [1] Tulane University

     Tulane University

     City of New Orleans, Estados Unidos

     
  2. [2] Louisiana State University

     Louisiana State University

     Estados Unidos

     
  3. [3] Anne Arundel Medical Center

     Anne Arundel Medical Center

     Estados Unidos

     
  4. [4] University of North Texas Health Science Center

     University of North Texas Health Science Center

     Estados Unidos

     
  5. [5] Tulane Center for Stem Cell Research and Regenerative Medicine, New Orleans, LA, USA
  6. [6] Molecular Devices LLC, San Jose, CA, USA
  7. [7] Protein Fluidics Inc, Burlingame, CA, USA
  8. [8] Department of Surgery, Section of Plastic & Reconstructive Surgery, Louisiana State University Health Sciences Center, New Orleans, LA, USA
  9. [9] Tulane Cancer Center, New Orleans, LA, USA
  10. [10] Innogenomics Technologies LLC, New Orleans, LA, USA
  11. [11] Louisiana Cancer Research Center, Biospecimen Core, New Orleans, LA, USA; Department of Pathology, Tulane University School of Medicine, New Orleans, LA, USA
  12. [12] Louisiana Cancer Research Center, Biospecimen Core, New Orleans, LA, USA; Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 24, Nº. 1 (Enero), 2022, págs. 127-144
• Idioma: inglés
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• Resumen

  • Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an indepth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofuorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu·MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stifness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell–matrix interactions in rare cancer types using higher passage PDX tissue.