{"doi":"10.1172/jci.insight.130751","title":"Fibroblast subtypes define a metastatic matrisome in breast cancer","abstract":"Small primary breast cancers can show surprisingly high potential for metastasis. Clinical decision-making for tumor aggressiveness, including molecular profiling, relies primarily on analysis of the cancer cells. Here we show that this analysis is insufficient - that the stromal microenvironment of the primary tumor plays a key role in tumor cell dissemination and implantation at distant sites. We previously described 2 cancer-associated fibroblasts (CAFs) that either express (CD146+) or lack (CD146-) CD146 (official symbol MCAM, alias MUC18). We now find that when mixed with human breast cancer cells, each fibroblast subtype determines the fate of cancer cells: CD146- fibroblasts promoted increased metastasis compared with CD146+ fibroblasts. Potentially novel quantitative and qualitative proteomic analyses showed that CD146+ CAFs produced an environment rich in basement membrane proteins, while CD146- CAFs exhibited increases in fibronectin 1, lysyl oxidase, and tenascin C, all overexpressed in aggressive disease. We also show clinically that CD146- CAFs predicted for likelihood of lymph node involvement even in small primary tumors (<5 cm). Clearly small tumors enriched for CD146- CAFs require aggressive treatments.","journal":"JCI Insight","year":2020,"id":94098,"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":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":234991,"name":"Alexander Barrett","orcid":"0000-0002-4979-3756","position":1,"is_corresponding":false},{"id":470477,"name":"Etana Kopin","orcid":null,"position":2,"is_corresponding":false},{"id":470478,"name":"Jaime Hagen","orcid":null,"position":3,"is_corresponding":false},{"id":469249,"name":"Amy Han","orcid":"0000-0002-1890-3510","position":4,"is_corresponding":false},{"id":225904,"name":"Austin E. Gillen","orcid":"0000-0003-2928-6308","position":5,"is_corresponding":false},{"id":381031,"name":"Jessica Finlay-Schultz","orcid":"0000-0002-7855-9870","position":6,"is_corresponding":false},{"id":267508,"name":"Diana M. Cittelly","orcid":"0000-0002-8392-0800","position":7,"is_corresponding":false},{"id":381721,"name":"Philip Owens","orcid":"0000-0002-1452-9285","position":8,"is_corresponding":false},{"id":292450,"name":"Kathryn B. Horwitz","orcid":"0000-0001-7402-6455","position":9,"is_corresponding":false},{"id":292451,"name":"Carol A. Sartorius","orcid":"0000-0002-9170-3988","position":10,"is_corresponding":false},{"id":11001,"name":"Kirk C. Hansen","orcid":"0000-0001-5054-838X","position":11,"is_corresponding":false},{"id":234998,"name":"Peter Kabos","orcid":"0000-0003-1500-471X","position":12,"is_corresponding":false},{"id":469248,"name":"Heather M. Brechbuhl","orcid":"0000-0003-3132-4465","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T22:32:04.778261Z","pmid":"32045383","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":[]}