Diabetic hyperglycemia promotes primary tumor progression through glycation-induced tumor extracellular matrix stiffening.

ABSTRACT: Diabetes mellitus is a complex metabolic disorder that is associated with an increased risk of breast cancer. Despite this correlation, the interplay between tumor progression and diabetes, particularly with regard to stiffening of the extracellular matrix, is still mechanistically unclear. Here, we established a murine model where hyperglycemia was induced before breast tumor development. Using the murine model, in vitro systems, and patient samples, we show that hyperglycemia increases tumor growth, extracellular matrix stiffness, glycation, and epithelial-mesenchymal transition of tumor cells. Upon inhibition of glycation or mechanotransduction in diabetic mice, these same metrics are reduced to levels comparable with nondiabetic tumors. Together, our study describes a novel biomechanic

SUBMITTER: Wang W 

PROVIDER: S-EPMC9674287 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature