title: Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes.
abstract: Five molecular subtypes (luminal A, luminal B, HER2-enriched, basal-like, and claudin-low) with clinical implications exist in breast cancer. Here, we evaluated the molecular and phenotypic relationships of (1) a large in vitro panel of human breast cancer cell lines (BCCLs), human mammary fibroblasts (HMFs), and human mammary epithelial cells (HMECs); (2) in vivo breast tumors; (3) normal breast cell subpopulations; (4) human embryonic stem cells (hESCs); and (5) bone marrow-derived mesenchymal stem cells (hMSC). First, by integrating genomic data of 337 breast tumor samples with 93 cell lines we were able to identify all the intrinsic tumor subtypes in the cell lines, except for luminal A. Secondly, we observed that the cell lines recapitulate the differentiation hierarchy detected in the normal mammary gland, with claudin-low BCCLs and HMFs cells showing a stromal phenotype, HMECs showing a mammary stem cell/bipotent progenitor phenotype, basal-like cells showing a luminal progenitor phenotype, and luminal B cell lines showing a mature luminal phenotype. Thirdly, we identified basal-like and highly migratory claudin-low subpopulations of cells within a subset of triple-negative BCCLs (SUM149PT, HCC1143, and HCC38). Interestingly, both subpopulations within SUM149PT were enriched for tumor-initiating cells, but the basal-like subpopulation grew tumors faster than the claudin-low subpopulation. Finally, claudin-low BCCLs resembled the phenotype of hMSCs, whereas hESCs cells showed an epithelial phenotype without basal or luminal differentiation. The results presented here help to improve our understanding of the wide range of breast cancer cell line models through the appropriate pairing of cell lines with relevant in vivo tumor and normal cell counterparts.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 450 West Drive, CB7295, Chapel Hill, NC, 27599, USA.
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.forename: Olga
authors.initials: O
authors.lastname: Karginova
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.forename: Xiaping
authors.initials: X
authors.lastname: He
authors.forename: Lisa
authors.initials: L
authors.lastname: Bixby
authors.forename: J Chuck
authors.initials: JC
authors.lastname: Harrell
authors.forename: Erick
authors.initials: E
authors.lastname: Roman
authors.forename: Barbara
authors.initials: B
authors.lastname: Adamo
authors.forename: Melissa
authors.initials: M
authors.lastname: Troester
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057167:Claudins / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012016:Reference Values; D017154:Stromal Cells / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D015415:Biomarkers; D057167:Claudins; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human