Diabetic hyperglycemia promotes primary tumor progression through glycation-induced tumor extracellular matrix stiffening
Menée in vitro et à l'aide d'un modèle murin de tumeur mammaire, cette étude met en évidence un mécanisme par lequel une hyperglycémie liée au diabète favorise la progression tumorale via le raidissement de la matrice extracellulaire induit par la glycation
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 biomechanical mechanism by which diabetic hyperglycemia promotes breast tumor progression via glycating the extracellular matrix. In addition, our work provides evidence that glycation inhibition is a potential adjuvant therapy for diabetic cancer patients due to the key role of matrix stiffening in both diseases. Diabetes-induced high blood glucose promotes breast cancer through glycation-mediated stiffening of tumor stroma.
Science Advances 2022