Evaluation of the Matrix Structure, Immunological Profile and Cellular Metabolism of Diabetic Breast Cancer Tumors

Abstract

Diabetes places women at a higher risk of developing breast cancer and is associated with increased mortality from the disease. However, the mechanisms by which diabetes promotes tumor formation and progression are not well understood. High blood glucose levels are known to glycate or crosslink collagen and increase tissue stiffness. Evidence from a recent study using a diabetic mouse model showed diabetic mice form stiffer and more aggressive breast cancer tumors. Elevated glucose levels have also been shown to increase cell proliferation and migration, alter cell metabolism, and increase inflammation levels. In this work we evaluate the impact of diabetes on 1) the collagen architecture of tumors 2) the level of immune infiltration into tumors and 3) the behavior of the cancer cells themselves. As a result, we found no difference in collagen alignment or architecture in diabetic versus non-diabetic breast tumors despite the increased stiffness of diabetic tumors. We also demonstrated that diabetic tumors have a reduced number of infiltrating CD45 and CD8 immune cells. On the question of the influence of diabetes on the cancer cells, we found that cells isolated from diabetic tumors have higher levels of proliferation and migration compared to cells from non-diabetic tumors. Cells from diabetic tumors also have higher levels of glucose uptake likely mediated by increased expression of glucose transporter GLUT1.