title: Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes.
abstract: Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1) and protumoral (M2) activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli.
authors.affiliation: Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, Colonia Doctores, 06720 Ciudad de México, DF, Mexico.
authors.forename: G Karina
authors.initials: GK
authors.lastname: Chimal-Ramírez
authors.affiliation: Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, Colonia Doctores, 06720 Ciudad de México, DF, Mexico; Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), 04510 Ciudad de México, DF, Mexico.
authors.forename: Nancy Adriana
authors.initials: NA
authors.lastname: Espinoza-Sánchez
authors.affiliation: UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, IMSS, 06720 Ciudad de México, DF, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Chávez-Sánchez
authors.affiliation: UIM en Inmunoquímica, Hospital de Especialidades, CMN Siglo XXI, IMSS, 06720 Ciudad de México, DF, Mexico.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Arriaga-Pizano
authors.affiliation: Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, Colonia Doctores, 06720 Ciudad de México, DF, Mexico.
authors.forename: Ezequiel M
authors.identifier: 0000-0003-2872-0459
authors.initials: EM
authors.lastname: Fuentes-Pananá
mesh_terms: D001119:Arginase / Q000235:genetics; D051940:B7-2 Antigen / Q000235:genetics; D053285:CD30 Ligand / Q000235:genetics; D018955:CD36 Antigens / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D010641:Phenotype; D054400:Receptors, CCR7 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D051940:B7-2 Antigen; C515370:CCR7 protein, human; D053285:CD30 Ligand; D018955:CD36 Antigens; C497964:CD86 protein, human; D016207:Cytokines; C576710:IDO1 protein, human; C508609:IL10 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D054400:Receptors, CCR7; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D001119:Arginase