The dynamic tumor–stromal crosstalk: implications of ‘stromal-hot’ tumors in the process of epithelial–mesenchymal transition in breast cancer

• Published in: Molecular biology reports Vol. 50; no. 6; pp. 5379 - 5393
• Main Authors: Mavatkar, Apoorva D., Naidu, Chandrakala M., Prabhu, Jyothi S., Nair, Madhumathy G.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-06-2023; Springer Nature B.V
• Subjects: Adipocytes; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Endothelial cells; Endothelial Cells - pathology; Epithelial-Mesenchymal Transition - genetics; Extracellular matrix; Extracellular Matrix Biology; Female; Fibroblasts; Histology; Humans; Life Sciences; Macrophages; Metastases; Metastasis; MicroRNAs - genetics; miRNA; Morphology; Protein seeding; Review; Secretome; Stromal cells; Stromal Cells - pathology; Tumor cells; Tumors; Tumor–stromal crosstalk; Epithelial–mesenchymal transition; Breast cancer; Metastasis; MicroRNAs
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-023-08422-4

Background:
Breast cancer metastatic programming involves an intricate process by which the tumor cell coevolves with the surrounding extracellular niche. The supporting cells from the local host stroma get transformed into cancer-associated stromal cells. This complex crosstalk leads to extracellular matrix remodeling, invasion, and eventually distant metastasis.
Methods:
In this review, we examine the protein-miRNA secretome that is crucial for this crosstalk. We also provide evidence from the literature for the pivotal role played by the various stromal cells like fibroblasts, adipocytes, and immune cells in promoting the process of EMT in breast cancer. Through in-silico analysis, we have also attempted to establish that stromal presence is integral to the process of EMT.
Results and Conclusion:
The in-silico analysis delineates the persuasive role of the stroma in mediating epithelial-to-mesenchymal transition. This review elucidates the importance of examining the role of the stromal niche that can yield promising diagnostic markers and pave avenues for formulating tailored anti-cancer therapy.
Graphical abstract
Process of EMT as driven by ‘stroma-hot’ tumors: The process of EMT is driven by the stromal cells. The stromal cells in the form of  fibroblasts, adipocytes, endothelial cells, mesenchymal stromal cells and tissue associated macrophages secrete the miRNA-protein secretome that modulates the stromal niche and the tumor cells to be become ‘tumor associated’. This drives tumor progression and invasion. The ‘stromal-hot’ tumors eventually get the benefit of the surplus nurturing from the stroma that facilitates EMT leading to distant organ seeding and metastasis