1. Cytokines in various molecular subtypes of breast cancer
- Author
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Vyacheslav V. Lyakhovich, Nikolay Varaksin, Alexsander Autenshlyus, Igor Marinkin, and Kristina Davletova
- Subjects
Pharmacology ,molecular subtypes ,business.industry ,Immunology ,Cancer ,Triple Negative Breast Neoplasms ,Disease ,medicine.disease ,Cell Line ,Breast cancer ,Invasive carcinoma of no special type ,invasive carcinoma of no special type ,Cell Line, Tumor ,medicine ,Cancer research ,Immunology and Allergy ,Cytokines ,Humans ,Female ,Original Research Article ,business ,mitogens - Abstract
Introduction Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and functional characteristics of a tumor in terms of cytokine secretion remains unknown. Methods We studied spontaneous and mitogen-induced cytokine secretion by invasive breast carcinoma of no special type (IBC NST; cultured tumors and cultured peripheral blood cells), depending on a molecular tumor subtype (where “mitogens” means “polyclonal activators” (PA): phytohemagglutinin p, phytohemagglutinin M, concanavalin A, and Escherichia coli lipopolysaccharide). Enzyme-linked immunosorbent assays were used to determine concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 in culture supernatants of the tumors and peripheral blood cells. Results The luminal B HER2-positive molecular subtype of IBC NST was found to feature the highest spontaneous secretion of IL-6 and IL-8 and the highest mitogen-induced secretion of IL-6, IL-8, IL-1Ra, and TNF-α by tumors; the highest mitogen-induced secretion of IL-2, IL-6, IL-8, IL-1β, TNF-α, IFN-γ, and G-CSF by peripheral blood cells; and the highest cytokine-producing potential (the ratio of mitogen-induced to spontaneous secretion) of peripheral blood cells for the secretion of IL-6, IL-8, and IL-1Ra as compared to other molecular subtypes. The triple-negative subtype of IBC NST was characterized by the lowest cytokine-producing potential of tumors for the secretion of IL-6 and IL-8 as compared to other molecular subtypes as well as a lower “stimulation index of polyclonal activators” (calculated as (cytokine secretion after incubation with PA)/(spontaneous cytokine secretion)) for IL-18 secretion as compared to luminal subtypes. The XYZ correlated with a suppressive effect of PA on cytokine secretion by tumors of the triple-negative molecular subtype. Conclusion Therefore, our findings indicate that in IBC NST of luminal B HER2-positive and triple-negative molecular subtypes, the cytokine network has distinctive functional features.
- Published
- 2021