Fig. 6: Lipid processing endothelial cells—translational implications.

a Schematic overview of the survival analysis in the retrospective clinical cohort and immunostaining validation. UH university hospital, BC breast cancer, HER2 human epidermal growth factor receptor 2, BMI body mass index, HR hormone receptor status. Color coding in the clinical characteristics panel reflects differences in age, BMI, tumor stage & grade (Supplementary Data 6). Color coding underneath the treatment stratification panel indicates patients that did (green) or did not (blue) receive metformin treatment during follow up. b Cumulative incidence function estimate of BC-specific survival (left panel) and the distant relapse free interval (right panel) in BC patients stratified by intake of a metformin. Color coded by group: blue – control, green – patients treated with metformin, purple – control matched for age, BMI, tumor stage & grade and hormone receptor status. P-values were calculated by the Kaplan–Meier (log rank) test between metformin therapy and without metformin therapy groups (blue for unmatched control patients; purple for matched control patients). Numbers in the boxes underneath the curves depict the number of patients per group that are at risk for the event (mortality in left panel, mortality/development of metastasis in right panel) at the indicated time points. c Quantification of FABP4⁺ blood vessels (% area of total CD105⁺ blood vessels) in non-diabetic BC patients (n = 8) and in diabetic patients without (n = 8) or with (n = 9) metformin treatment. Data are mean ± SEM, **p < 0.01 (exact p-values = 0.0030 and 0.0023, respectively), one-way ANOVA followed by Dunnett’s multiple comparisons test. d Representative micrographs of human breast tumor tissue sections in control non-diabetic (left; n = 8) or diabetic (middle; n = 8) control BC patients and in (diabetic) BC patients treated with metformin (right; n = 9), immunostained for CD105, FABP4 and counterstained with Hoechst. Arrowheads denote CD105⁺FABP4⁺ vessels, asterisks denote (putative) adipocytes, which (besides LIPECs) are also positive for FABP4. Brightness was increased linearly (gamma = 1) to improve visibility for CD105 and FABP4. Scale bar: 75 µm.