title: Cytokine profiles of tumor supernatants in invasive ductal cancer and fibroadenoma of the breast and its relationship with VEGF-A expression in the tumors.
abstract: Interrelations between cytokines, produced by invasive ductal carcinoma (IDC) and fibroadenoma (FA) of the breast, and angiogenic growth factor VEGF-A, expressed in IDC and FA, were investigated. The analysis of the cytokine profiles of IDC and FA was performed by cultivation of tumor biopsy specimens in vitro. Testing of the cytokine-producing reserve of the tumors for production of VEGF-A was conducted by culturing samples of IDC and FA in a medium containing polyclonal activator (a complex of phytohemagglutinin, concanavalin A, and lipopolysaccharide). Levels of cytokines and growth factors (IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A) and MCP-1 (monocyte chemoattractant protein-1) in tumor supernatants were determined by an ELISA. Expression of VEGF-A was analyzed in tumor biopsy specimens by immunohistochemical analysis. In the IDC supernatants, the concentrations of IL-17, IL-18, and IFN-γ were higher and the concentrations of IL-10 and MCP-1 were lower in comparison with the FA supernatants. We observed negative correlations between the macrophage infiltration and VEGF-A concentration in the IDC supernatants (r = -0.508; P = 0.011) and between VEGF-A expression and the IDC vascularization degree (r = -0.423, P = 0.039). Spontaneous expression of VEGF-A in samples of IDC significantly exceeded the VEGF-A expression in FA. There was no difference between IDC and FA in VEGF-A expression after treatment with the polyclonal activators. Our results indicate that greater malignancy may have a paradoxical effect that is controlled by cytokines and characterized by weakening of tumor angiogenesis during overproduction of VEGF-A. These findings point to complex mechanisms of positive and negative regulation of tumor angiogenesis by cytokines that are produced by the tumor and by cells in its microenvironment, whose cytokine profiles may change at different stages of tumor progression.
authors.affiliation: 1 Novosibirsk State Medical University, Novosibirsk, Russia.|2 Institute of molecular biology and Biophysics, Novosibirsk, Russia.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Autenshlyus
authors.affiliation: 1 Novosibirsk State Medical University, Novosibirsk, Russia.|2 Institute of molecular biology and Biophysics, Novosibirsk, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Arkhipov
authors.affiliation: 1 Novosibirsk State Medical University, Novosibirsk, Russia.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Kunts
authors.affiliation: 1 Novosibirsk State Medical University, Novosibirsk, Russia.
authors.forename: Igor O
authors.initials: IO
authors.lastname: Marinkin
authors.affiliation: 1 Novosibirsk State Medical University, Novosibirsk, Russia.|2 Institute of molecular biology and Biophysics, Novosibirsk, Russia.
authors.forename: Elena S
authors.initials: ES
authors.lastname: Mikhailova
authors.affiliation: 2 Institute of molecular biology and Biophysics, Novosibirsk, Russia.
authors.forename: Xenia V
authors.initials: XV
authors.lastname: Karpukhina
authors.affiliation: 3 AO Vector-best, Novosibirsk, Russia.
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Varaksin
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D018226:Fibroadenoma / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: breast; cancer; cytokines; fibroadenoma