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Breast Cancer Tumor Stroma: Cellular Components, Phenotypic Heterogeneity, Intercellular Communication, Prognostic Implications and Therapeutic Opportunities

1
Research Unit, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain
2
Department of Anatomical Pathology, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain
3
Department of Obstetrics and Gynecology, Universidad Rey Juan Carlos, Avda. de Atenas s/n, 28922, Alcorcón, Madrid, Spain
4
Department of Surgery, Fundación Hospital de Jove, Avda. Eduardo Castro, 161, 33290 Gijón, Spain
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(5), 664; https://doi.org/10.3390/cancers11050664
Received: 12 April 2019 / Revised: 7 May 2019 / Accepted: 8 May 2019 / Published: 13 May 2019
(This article belongs to the Special Issue The Role of Integrins in Cancer)
PDF [622 KB, uploaded 13 May 2019]
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Abstract

Although the mechanisms underlying the genesis and progression of breast cancer are better understood than ever, it is still the most frequent malignant tumor in women and one of the leading causes of cancer death. Therefore, we need to establish new approaches that lead us to better understand the prognosis of this heterogeneous systemic disease and to propose new therapeutic strategies. Cancer is not only a malignant transformation of the epithelial cells merely based on their autonomous or acquired proliferative capacity. Today, data support the concept of cancer as an ecosystem based on a cellular sociology, with diverse components and complex interactions between them. Among the different cell types that make up the stroma, which have a relevant role in the dynamics of tumor/stromal cell interactions, the main ones are cancer associated fibroblasts, endothelial cells, immune cells and mesenchymal stromal cells. Several factors expressed by the stroma of breast carcinomas are associated with the development of metastasis, such as matrix metalloproteases, their tissular inhibitors or some of their regulators like integrins, cytokines or toll-like receptors. Based on the expression of these factors, two types of breast cancer stroma can be proposed with significantly different influence on the prognosis of patients. In addition, there is evidence about the existence of bi-directional signals between cancer cells and tumor stroma cells with prognostic implications, suggesting new therapeutic strategies in breast cancer.
Keywords: CAFs; MMPs; TIMPs; cytokines; TLRs; mesenchymal stromal cells; exosomes; integrins CAFs; MMPs; TIMPs; cytokines; TLRs; mesenchymal stromal cells; exosomes; integrins
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Eiro, N.; Gonzalez, L.O.; Fraile, M.; Cid, S.; Schneider, J.; Vizoso, F.J. Breast Cancer Tumor Stroma: Cellular Components, Phenotypic Heterogeneity, Intercellular Communication, Prognostic Implications and Therapeutic Opportunities. Cancers 2019, 11, 664.

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