Cytokines in various molecular subtypes of breast cancer.

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.

• Authors: Alexsander Autenshlyus, Kristina Davletova, Nikolay Varaksin, Igor Marinkin, Vyacheslav Lyakhovich
• Journal: International journal of immunopathology and pharmacology (Int J Immunopathol Pharmacol) 2021 Jan-Dec Vol. 35 Pg. 20587384211034089 ISSN: 2058-7384 [Electronic] England
• PMID: 34399595 (Publication Type: Journal Article)

Chemical References

• Cytokines

Topics

• Cell Line
• Cell Line, Tumor
• Cytokines (metabolism)
• Female
• Humans
• Triple Negative Breast Neoplasms (metabolism, pathology)