The Tumor Microenvironment of Primitive and Metastatic Breast Cancer: Implications for Novel Therapeutic Strategies
Abstract
:1. Introduction
2. Primary Breast Cancer Microenvironment
2.1. Breast Cancer-Associated Fibroblasts
2.1.1. TGF-β1 (Transforming Growth Factor β1)
2.1.2. HGF (Hepatocyte Growth Factor)
2.1.3. IL32 (Interleukin 32)
2.1.4. IL6 (Interleukin 6)
2.2. Breast Cancer-Associated Leukocytes
2.3. Breast Cancer-Associated Endothelium
2.4. Breast Cancer-Associated Mesenchymal Stem Cells
2.5. Breast Cancer-Associated Extracellular Matrix
3. Engineered Breast Cancer Models
TME Component | Main Functions | Ref. |
---|---|---|
Fibroblasts | Promotion of EMT. Enhancement of proliferation rate. Induction of ECM remodeling. Lowering of apoptotic rate. Promotion of angiogenesis. | [10,11,12,13,14,15,16,17,18] |
Macrophages | Promotion of angiogenesis. Immunosuppression. Promotion of EMT. Enhancement of cancer motility. | [21,22,23,24] |
Lymphocytes | Deregulation of immune checkpoints in favor of immunosuppression. | [24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53] |
Endothelial cells | Angiogenesis Enhanced proliferation rate and metastatic potential through paracrine signaling. | [57,58,59] |
Mesenchymal stem cells | Enhancement of proliferation rate via exosomes. Immunosuppression. Induction of dormancy through cannibalization. | [60,61,62,63,64,65,66,67,68,69] |
Extracellular matrix | Enhancement of cancer motility. | [71,72,73,74,75,76,77] |
4. Interaction Mechanisms in the Breast Cancer Tumor Microenvironment
5. Metastatic Breast Cancer Microenvironment
6. Relationship between the Microenvironment and the Molecular Subtypes of Breast Cancer
7. Therapeutic Implications
8. Conclusions
Funding
Conflicts of Interest
References
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Zarrilli, G.; Businello, G.; Dieci, M.V.; Paccagnella, S.; Carraro, V.; Cappellesso, R.; Miglietta, F.; Griguolo, G.; Guarneri, V.; Lo Mele, M.; et al. The Tumor Microenvironment of Primitive and Metastatic Breast Cancer: Implications for Novel Therapeutic Strategies. Int. J. Mol. Sci. 2020, 21, 8102. https://doi.org/10.3390/ijms21218102
Zarrilli G, Businello G, Dieci MV, Paccagnella S, Carraro V, Cappellesso R, Miglietta F, Griguolo G, Guarneri V, Lo Mele M, et al. The Tumor Microenvironment of Primitive and Metastatic Breast Cancer: Implications for Novel Therapeutic Strategies. International Journal of Molecular Sciences. 2020; 21(21):8102. https://doi.org/10.3390/ijms21218102
Chicago/Turabian StyleZarrilli, Giovanni, Gianluca Businello, Maria Vittoria Dieci, Silvia Paccagnella, Valentina Carraro, Rocco Cappellesso, Federica Miglietta, Gaia Griguolo, Valentina Guarneri, Marcello Lo Mele, and et al. 2020. "The Tumor Microenvironment of Primitive and Metastatic Breast Cancer: Implications for Novel Therapeutic Strategies" International Journal of Molecular Sciences 21, no. 21: 8102. https://doi.org/10.3390/ijms21218102