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Systemic Evaluation of the Effect of Diabetes Mellitus on Breast Cancer in a Mouse Model
Nana Wei1, Jinmiao Lu2, Zhibing Lin3
1Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai, China.
Abstract:
Breast cancer complicated with diabetes mellitus (DM) is a common disease. To evaluate the effect of preexisting DM on breast cancer progression without drug interference, we used a streptozotocin (STZ)-induced type 2 diabetes mellitus BALB/c mouse model. We found that 4T1 breast cancer complicated with DM decreased the mouse survival time compared with 4T1-bearing mice. The diversity of gut microbiome was affected by DM. The infiltration of mucosal-associated invariant T cell (MAIT), CD8+ T cell, and CD4+ T cell in the tumor was significantly decreased in the DM-4T1 group compared with the 4T1 group. The transcriptome data of tumor tissues indicated that the expressions of inflammatory C-C chemokine- and metabolism-related genes were greatly changed. The abnormal expression of these genes may be related with the decreased T-cell infiltration in DM-4T1. In conclusion, the gut microbiome and tumor microenvironment of diabetic breast cancer patients have unique features. The effect of diabetes on breast cancer should be considered in the treatment for diabetic breast cancer patients.
Insights
Diabetes mellitus (DM) worsens breast cancer outcomes, reducing survival time and altering the gut microbiome. Diabetic conditions also decrease crucial T-cell infiltration in tumors, impacting cancer progression.
Area of Science:
- Oncology
- Immunology
- Metabolism
Background:
- Breast cancer and diabetes mellitus (DM) frequently coexist.
- DM's impact on breast cancer progression, independent of drug effects, requires investigation.
Purpose of the Study:
- To evaluate how preexisting type 2 diabetes mellitus affects breast cancer progression.
- To analyze changes in gut microbiome, immune cell infiltration, and gene expression in a diabetic breast cancer model.
Main Methods:
- Utilized a streptozotocin (STZ)-induced type 2 diabetes mellitus BALB/c mouse model.
- Compared 4T1 breast cancer progression in diabetic versus non-diabetic mice.
- Analyzed gut microbiome diversity, tumor-infiltrating immune cells (MAIT, CD8+, CD4+ T cells), and tumor tissue transcriptomes.
Main Results:
- Diabetic mice with 4T1 breast cancer showed reduced survival compared to non-diabetic controls.
- DM significantly altered gut microbiome diversity.
- Tumor immune cell infiltration (MAIT, CD8+, CD4+ T cells) was markedly decreased in the diabetic group.
- Tumor transcriptome analysis revealed significant changes in inflammatory chemokine and metabolism-related gene expressions.
Conclusions:
- Diabetes mellitus uniquely impacts the gut microbiome and tumor microenvironment in breast cancer.
- Altered gene expression in diabetic breast cancer may contribute to reduced T-cell infiltration.
- The influence of diabetes on breast cancer necessitates consideration in clinical treatment strategies for diabetic patients.
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