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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
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732292/ https://www.ncbi.nlm.nih.gov/pubmed/34370182 http://dx.doi.org/10.1007/s12094-021-02677-8 |
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author | Matossian, M. D. Chang, T. Wright, M. K. Burks, H. E. Elliott, S. Sabol, R. A. Wathieu, H. Windsor, G. O. Alzoubi, M. S. King, C. T. Bursavich, J. B. Ham, A. M. Savoie, J. J. Nguyen, K. Baddoo, M. Flemington, E. Sirenko, O. Cromwell, E. F. Hebert, K. L. Lau, F. Izadpanah, R. Brown, H. Sinha, S. Zabaleta, J. Riker, A. I. Moroz, K. Miele, L. Zea, A. H. Ochoa, A. Bunnell, B. A. Collins-Burow, B. M. Martin, E. C. Burow, M. E. |
author_facet | Matossian, M. D. Chang, T. Wright, M. K. Burks, H. E. Elliott, S. Sabol, R. A. Wathieu, H. Windsor, G. O. Alzoubi, M. S. King, C. T. Bursavich, J. B. Ham, A. M. Savoie, J. J. Nguyen, K. Baddoo, M. Flemington, E. Sirenko, O. Cromwell, E. F. Hebert, K. L. Lau, F. Izadpanah, R. Brown, H. Sinha, S. Zabaleta, J. Riker, A. I. Moroz, K. Miele, L. Zea, A. H. Ochoa, A. Bunnell, B. A. Collins-Burow, B. M. Martin, E. C. Burow, M. E. |
author_sort | Matossian, M. D. |
collection | PubMed |
description | 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 in-depth 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 immunofluorescence 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 stiffness 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12094-021-02677-8. |
format | Online Article Text |
id | pubmed-8732292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-87322922022-01-06 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 Matossian, M. D. Chang, T. Wright, M. K. Burks, H. E. Elliott, S. Sabol, R. A. Wathieu, H. Windsor, G. O. Alzoubi, M. S. King, C. T. Bursavich, J. B. Ham, A. M. Savoie, J. J. Nguyen, K. Baddoo, M. Flemington, E. Sirenko, O. Cromwell, E. F. Hebert, K. L. Lau, F. Izadpanah, R. Brown, H. Sinha, S. Zabaleta, J. Riker, A. I. Moroz, K. Miele, L. Zea, A. H. Ochoa, A. Bunnell, B. A. Collins-Burow, B. M. Martin, E. C. Burow, M. E. Clin Transl Oncol Research Article 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 in-depth 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 immunofluorescence 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 stiffness 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12094-021-02677-8. Springer International Publishing 2021-08-09 2022 /pmc/articles/PMC8732292/ /pubmed/34370182 http://dx.doi.org/10.1007/s12094-021-02677-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Matossian, M. D. Chang, T. Wright, M. K. Burks, H. E. Elliott, S. Sabol, R. A. Wathieu, H. Windsor, G. O. Alzoubi, M. S. King, C. T. Bursavich, J. B. Ham, A. M. Savoie, J. J. Nguyen, K. Baddoo, M. Flemington, E. Sirenko, O. Cromwell, E. F. Hebert, K. L. Lau, F. Izadpanah, R. Brown, H. Sinha, S. Zabaleta, J. Riker, A. I. Moroz, K. Miele, L. Zea, A. H. Ochoa, A. Bunnell, B. A. Collins-Burow, B. M. Martin, E. C. Burow, M. E. 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732292/ https://www.ncbi.nlm.nih.gov/pubmed/34370182 http://dx.doi.org/10.1007/s12094-021-02677-8 |
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