Figure 6. IL-1β and LCN2 play important roles in MGDAs-mediated tumorigenicity enhancement.

(a) MDA-MB-231 cells were supplemented with recombinant IL-1β and LCN2 in soft agar colony formation assays. (b). Soft agar colony formation assays showed that knockdown of LCN2 combining IL-1β neutralizing antibody treatment (αIL-1β, 1 μg ml⁻¹) significantly abrogated the increase of colonies induced by MGDAs co-culture with MDA-MB-231 cells. Mouse IgG (1 μg ml⁻¹) was used as a control. The experiments in a,b were performed in technical triplicate and repeated at least twice with similar results. Data show means±s.d. *P<0.05 (Student's t-test). (c) Schematic shows the heterotypic interaction between MGDAs and MCT2-expressing breast cancer cells in the breast tissue microenvironment. MGDAs promote the tumorigenicity of MCT2-expressing breast cancer cells in a paracrine manner. β-hydroxybutyrate secreted from MGDAs can be transported into breast cancer cells via MCT2. Intracellular β-hydroxybutyrate functions as a class I HDAC inhibitor and induces the expression of tumour-promoting genes through epigenetic modification, leading to tumorigenicity enhancement.