Tumour microenvironment markers in spontaneous and induced incubation of breast cancer biopsies

Aim. To study the spontaneous and stimulated production of cytokines in biopsies of breast cancer (BC) depending on the cancer stage.

Materials and methods. An experimental study was carried out with cell cultures of breast cancer biopsies of stages I–II (group 1, n = 15) and III–IV stages (group 2, n = 15). The control consisted of 6 healthy women who underwent mastopexy. We used enzyme immunoassay method to access spontaneous and induced by a complex of polyclonal activators (PA: phytohemagglutinin 4 μg / ml, concanavalin A 4 μg / ml, lipopolysaccharide 2 μg / ml) concentration of TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, MCP-1, TGF-β1. The index of the effect of polyclonal activators (IVPA) on cytokine production (induced production / spontaneous production) was calculated. To compare groups, the Mann-Whitney test and the median test, the chi-square test and the Fisher’s exact test were used.

Results. Groups 1 and 2 did not differ in age, histological variant and immunohistochemical type of tumour, predominantly invasive cancer without signs of specificity prevailed. In group 2, a pronounced vascularization was more often observed: in 6 (40%) patients versus 1 (7%) in group 1 (p < 0.05). In both groups, compared with the control, there was a statistically sig-nificant (p < 0.05) increase in spontaneous production of TNF-α by 4.2 and 4.8 times, MCP-1 by 6.7 and 6.3 times, TGF-β1 – 2.2 and 2.5 times, VEGF 11.9 and 14.6 times; GM-CSF 15.6 and 13.4 times, G-CSF 96.8 and 79.5 times, respectively. The concentration of MCP-1 and IFN-γ was higher in group 1 (p < 0.05), VEGF and TGF-β1 – in group 2 (p < 0.05). IVPA in group 2 exceeded similar values   in group 1 for G-CSF, VEGF, TGF-β1 (p < 0.05).

Conclusion. The production of cytokines (TNF-α, MCP-1, GM-CSF, G-CSF, VEGF, TGF-β1) in breast cancer biopsies is significantly higher than in biopsies of the unchanged mammary gland and depends on the stage of the tumour process.

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