Polarization effect of group 2 innate lymphoid cells in breast cancer

Abstract:

Objective：To investigate the role of group 2 innate lymphoid cells（ILC2） and its transcription factors and products in the breast cancer（BC）. Methods：The peripheral blood from healthy subjects and BC patients（at early and advanced stage） was collect－ed. The peripheral blood mononuclear cell（PBMC） was isolated and the level of ILC2 in PBMC was detected by flow cytometry. Total RNA was extracted from PBMC. The gene expression level of specific transcription factor（GATA3 and RORα） and ILC2 production （IL-13 and IL-4），which regulated ILC2 development，was detected. The protein expression of T-helper 2 cytokine in serum（IL-13，IL-4，IL-33 and IL-10） were detected. Exogenous IL-13 and IL-4 were used to stimulate MCF-7 and MDA-MB 231 cancer cells，so as to simulate the polarization effect of ILC2 in BC patients：detecting the proliferation activity of cancer cells，detecting changes of protein expression of proliferation and autophagy signal factors；observing cell apoptosis via flow cytometry and fluorescence micro－scope. Results：ILC2 level in peripheral circulation of BC patients was increased（normal group vs. early stage group，0.019 6% vs. 0.028 9%，P=0.008；normal group vs. advanced stage group，0.019 6% vs. 0.027 3%，P=0.032）. Estrogen/progesterone expression status was an important factor influencing ILC2 level（HR=0.436，P=0.038）. The expression of GATA3，RORα，IL-13，IL-4，IL-33 and IL-10 was increased with tumor burden aggravation（P<0.05）. Com－bined stimulation of exogenous IL-13 and IL-4 was able to en－hance the proliferation viability of BC cells by up-regulating ERK1/2 and pERK1/2（P=0.000）. Combined stimulation was able to induce the expression of autophagy signaling molecules of MCF-7 and MDA-MB 231 cells（P=0.000） and to induce the apoptosis of MDA-MB 231 cells（P=0.000），but it had no obvious induction for the apoptosis of MCF-7 cells（P>0.05）. Conclusion：The increased proportion of ILC2 in peripheral circulation and the increased expression of up-and-down-stream factors of ILC2 is re－lated to the oncogenesis and development of BC.