{"doi":"10.1007/s12094-021-02677-8","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","abstract":"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.","journal":"Clinical & Translational Oncology","year":2021,"id":175638,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.916,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":376489,"name":"Tiffany Chang","orcid":"0000-0002-0468-7546","position":1,"is_corresponding":false},{"id":450050,"name":"Maryl Wright","orcid":null,"position":2,"is_corresponding":false},{"id":376492,"name":"Hope E. 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Savoie","orcid":null,"position":12,"is_corresponding":false},{"id":448847,"name":"Khoa Nguyen","orcid":"0000-0002-8059-6136","position":13,"is_corresponding":false},{"id":445951,"name":"Melody Baddoo","orcid":"0000-0001-8501-9728","position":14,"is_corresponding":false},{"id":402648,"name":"Erik K. Flemington","orcid":"0000-0003-0513-5281","position":15,"is_corresponding":false},{"id":592972,"name":"Oksana Sirenko","orcid":null,"position":16,"is_corresponding":false},{"id":592230,"name":"Evan F. Cromwell","orcid":"0000-0003-2935-0680","position":17,"is_corresponding":false},{"id":669353,"name":"Katherine Hebert","orcid":"0000-0002-7221-1857","position":18,"is_corresponding":false},{"id":448849,"name":"Frank H. Lau","orcid":"0000-0001-7061-4209","position":19,"is_corresponding":false},{"id":442093,"name":"Reza Izadpanah","orcid":"0000-0002-4520-8150","position":20,"is_corresponding":false},{"id":717483,"name":"Hiromi Brown","orcid":null,"position":21,"is_corresponding":false},{"id":716867,"name":"Sudhir K. Sinha","orcid":"0000-0002-0196-1941","position":22,"is_corresponding":false},{"id":107684,"name":"Jovanny Zabaleta","orcid":"0000-0002-5961-6761","position":23,"is_corresponding":false},{"id":377718,"name":"Adam I. Riker","orcid":null,"position":24,"is_corresponding":false},{"id":448850,"name":"Krzysztof Moroz","orcid":"0000-0002-2201-2876","position":25,"is_corresponding":false},{"id":376496,"name":"Lucio Miele","orcid":"0000-0002-5853-7287","position":26,"is_corresponding":false},{"id":448848,"name":"Arnold H. Zea","orcid":"0000-0002-1272-0027","position":27,"is_corresponding":false},{"id":640736,"name":"Augusto C. 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Matossian","orcid":"0000-0002-9527-1043","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:47:15.431199Z","pmid":"34370182","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}