Background: Type 2 diabetes increases incidence, progression, and death in breast cancer (BC) patients. Hyperglycemia acts on tumor microenvironment that in mammary gland is represented by adipose tissue (AT). AT releases signaling molecules such as cytokines, growth factors, and components of the extracellular matrix involved in the stroma-tumor cells crosstalk, but metabolic alterations, as high levels of glucose, impaired these processes. Versican (VCAN) is a chondroitin sulfate proteoglycan expressed in adipose tissue, with a key role in diabetic kidney and bone disease. Aim: Aim of our work is the study of AT-produced VCAN in the connection between diabetes and BC progression. Materials and methods: Mesenchymal stem cells (MSC) have been isolated from MAT biopsies of healthy women (H-MAT; N=16) and co-cultured with MCF7 BC cells. Conditioned medium from co-culture experiments was analyzed with ELISA Multiplex. VCAN content was investigated by IHC in peritumoral mammary-AT (C-MAT N=15). Total RNA and protein lysates have been analyzed by qPCR and Western blot analysis. Data were analyzed using GraphPad Prism 7. Result: In MSC isolated from H-MAT, VCAN mRNA and protein levels positively correlated with patients glycemia. MSC expressing high levels of VCAN displayed increase of Vascular Endothelial Growth Factor (VEGF) and Interleukin 6 (IL6) levels when co-coltured with MCF7, which in turn showed increase of Matrix metalloproteinase-9 (MMP-9). VCAN was detected in C-MAT at higher extent in the proximity of the tumor, compared to more distant sites and correlated with tumor Recurrence Score. Conclusion: VCAN positively correlates with glycemia in adipose progenitors. Its higher expression in MSC is correlated with angiogenesis and inflammation markers, suggesting a role in the connection between T2D and BC. Characterization of VCAN in AT surrounding BC may suggest a novel biomarker associated to BC progression in metabolically perturbed patients.