Original Articles

Stage-specific tumor microenvironment dynamics and cancer-associated fibroblast profiling in MBL-6 mouse models of breast cancer

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Published: 10 October 2025
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Breast cancer remains the most prevalent malignancy among women, necessitating the development of novel therapeutic strategies. Experimental animal models that closely mimic human breast cancer are crucial for advancing these therapies. This study utilized the criteria of the tumour, node, metastasis (TNM) staging system and variations in metabolic rates to develop models representing stages II and IV of human breast cancer, using the MBL-6 mouse breast cancer cell line. We assessed tumor growth curves in vivo and investigated distant metastasis to organs such as the liver, lungs, lymph nodes, and spleen. Carcinoma-associated fibroblasts (CAFs) were isolated, and their proliferation rates, inflammatory enzyme expression, and matrix metalloproteinase levels were compared between stages II and IV. By analyzing tumor kinetics and metabolic differences, we were able to predict tumor size and progression at each stage. Our results revealed that CAFs isolated from both stages exhibited similar phenotypic characteristics. However, CAFs from stage II tumors showed higher expression of indoleamine 2,3-dioxygenase 1 (IDO1), while those from stage IV tumors had higher levels of inducible nitric oxide synthase (iNOS). These distinct expression patterns suggest unique microenvironmental features at different stages of tumor progression. Further investigation of the cancer microenvironment may provide valuable insights for selecting targeted therapies and improving disease management.

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Supporting Agencies

This study was funded by the Research Deputy of Tarbiat Modares University.

How to Cite



Stage-specific tumor microenvironment dynamics and cancer-associated fibroblast profiling in MBL-6 mouse models of breast cancer. (2025). Veterinary Science Development, 9(1). https://doi.org/10.4081/vsd.2025.10069