title: Immunophenotyping and Transcriptomic Outcomes in PDX-Derived TNBC Tissue.
abstract: Cancer tissue functions as an ecosystem of a diverse set of cells that interact in a complex tumor microenvironment. Genomic tools applied to biopsies in bulk fail to account for this tumor heterogeneity, whereas single-cell imaging methods limit the number of cells which can be assessed or are very resource intensive. The current study presents methods based on flow cytometric analysis and cell sorting using known cell surface markers (CXCR4/CD184, CD24, THY1/CD90) to identify and interrogate distinct groups of cells in triple-negative breast cancer clinical biopsy specimens from patient-derived xenograft (PDX) models. The results demonstrate that flow cytometric analysis allows a relevant subgrouping of cancer tissue and that sorting of these subgroups provides insights into cancer cell populations with unique, reproducible, and functionally divergent gene expression profiles. The discovery of a drug resistance signature implies that uncovering the functional interaction between these populations will lead to deeper understanding of cancer progression and drug response.Implications:PDX-derived human breast cancer tissue was investigated at the single-cell level, and cell subpopulations defined by surface markers were identified which suggest specific roles for distinct cellular compartments within a solid tumor.Mol Cancer Res; 15(4); 429-38. ©2016 AACR.
authors.affiliation: BD Technologies, Research Triangle Park, Durham, North Carolina.
authors.forename: Eileen
authors.initials: E
authors.lastname: Snowden
authors.affiliation: BD Technologies, Research Triangle Park, Durham, North Carolina.
authors.forename: Warren
authors.initials: W
authors.lastname: Porter
authors.affiliation: BD Technologies, Research Triangle Park, Durham, North Carolina.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Hahn
authors.affiliation: BD Technologies, Research Triangle Park, Durham, North Carolina.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Ferguson
authors.affiliation: BD Technologies, Research Triangle Park, Durham, North Carolina.
authors.forename: Frances
authors.initials: F
authors.lastname: Tong
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.|Department of Genetics, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: BD Biosciences, San Jose, California.
authors.forename: Aaron
authors.initials: A
authors.lastname: Middlebrook
authors.affiliation: BD Biosciences, San Jose, California.
authors.forename: Smita
authors.initials: S
authors.lastname: Ghanekar
authors.affiliation: BD Technologies, Research Triangle Park, Durham, North Carolina.
authors.forename: W Shannon
authors.initials: WS
authors.lastname: Dillmore
authors.affiliation: BD Technologies, Research Triangle Park, Durham, North Carolina. rblaesius@bd.com.
authors.forename: Rainer
authors.initials: R
authors.lastname: Blaesius
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D051379:Mice; D009368:Neoplasm Transplantation; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000378:metabolism; D059010:Single-Cell Analysis / Q000379:methods*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000276:immunology*
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4