Breast cancer carcinoma-associated fibroblasts differ from breast fibroblasts in immunological and extracellular matrix regulating pathways.
Tumor stroma has been recently shown to play a crucial role in the development of breast cancer. Since the origin of the stromal cells in the tumor is unknown, we have examined differences and similarities between three stromal cell types of mesenchymal origin, namely carcinoma associated fibroblasts from breast tumor (CAFs), fibroblasts from normal breast area (NFs) and bone marrow derived mesenchymal stromal cells (MSCs). In a microarray analysis, immunological, developmental and extracellular matrix -related pathways were over-represented in CAFs when compared to NFs (p<0.001). Under hypoxic conditions, the expression levels of pyruvate dehydrogenase kinase-1 (PDK1) and pyruvate dehydrogenase kinase-4 (PDK4) were lower in CAFs when compared to NFs (fold changes 0.6 and 0.4, respectively). In normoxia, when compared to NFs, CAFs displayed increased expression of glucose transporter 1 (GLUT-1) and PDK1 (fold changes 1.5 and 1.3, respectively). With respect to the assessed surface markers, only CD105 was expressed differently in MSCs when compared to fibroblasts, being more often expressed on MSCs. Cells with myofibroblast features were present in both NF and CAF samples. We conclude, that CAFs differ distinctly from NFs at the gene expression level, this hypothesis was also tested in silico for other available gene expression data.
Cancer and Translational Medicine Research Unit, Medical Research Center Oulu (MRC Oulu), University of Oulu and Oulu University Hospital, P.O. BOX 5000, Oulu FIN-90014, Finland; Department of Anatomy and Cell Biology, Oulu University Hospital, Finland. Electronic address: ilkka.pasanen@oulu.fi.
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I
Pasanen
Cancer and Translational Medicine Research Unit, Medical Research Center Oulu (MRC Oulu), University of Oulu and Oulu University Hospital, P.O. BOX 5000, Oulu FIN-90014, Finland; Department of Anatomy and Cell Biology, Oulu University Hospital, Finland; Department of Internal Medicine, Oulu University Hospital, Finland.
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Lehtonen
Biocenter Oulu and Departments of Pathology, University of Oulu and Oulu University Hospital, Oulu, Finland.
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R
Sormunen
Biocenter Oulu, University of Oulu, Finland; Center for Life Course Epidemiology and Systems Medicine, Faculty of Medicine, University of Oulu, Finland; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland; Oulu Center for Cell - Matrix Research, University of Oulu, Finland.
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Skarp
Cancer and Translational Medicine Research Unit, Medical Research Center Oulu (MRC Oulu), University of Oulu and Oulu University Hospital, P.O. BOX 5000, Oulu FIN-90014, Finland.
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E
Lehtilahti
Turku Centre for Biotechnology, University of Turku, Turku FIN-20520, Finland.
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Pietilä
Department of Radiology, Oulu University Hospital, Finland.
R Blanco
RB
Sequeiros
Cancer and Translational Medicine Research Unit, Medical Research Center Oulu (MRC Oulu), University of Oulu and Oulu University Hospital, P.O. BOX 5000, Oulu FIN-90014, Finland; Department of Anatomy and Cell Biology, Oulu University Hospital, Finland; Department of Surgery, Oulu University Hospital, Finland.
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Lehenkari
Cancer and Translational Medicine Research Unit, Medical Research Center Oulu (MRC Oulu), University of Oulu and Oulu University Hospital, P.O. BOX 5000, Oulu FIN-90014, Finland; Department of Pathology, Oulu University Hospital, Finland.
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Kuvaja
D050156:Adipogenesis / Q000187:drug effects; D000328:Adult; D000368:Aged; D000818:Animals; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D000072645:Cancer-Associated Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000473:pathology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D003094:Collagen / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005782:Gels; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism; D008875:Middle Aged; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D014019:Tissue Donors; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005782:Gels; D016212:Transforming Growth Factor beta; D003094:Collagen
Breast cancer; Carcinoma-associated fibroblast; Hypoxia; Mesenchymal stromal cell; Microarray; Myofibroblast