Extracellular vesicle-mediated transport: Reprogramming a tumor microenvironment conducive with breast cancer progression and metastasis

Emerging evidence has shown multiple roles of the tumor microenvironment (TME) components, specifically the extracellular matrix (ECM), in breast cancer development, progression, and metastasis. Aside from the biophysical properties and biochemical composition of the breast ECM, the signaling molecules are extremely important in maintaining homeostasis, and in the breast TME, they serve as the key components that facilitate tumor progression and immune evasion. Extracellular vesicles (EVs), the mediators that convey messages between the cells and their microenvironment through signaling molecules, have just started to capture attention in breast cancer research. In this comprehensive review, we first provide an overview of the impact of ECM in breast cancer progression as well as the alterations occurring in the TME during this process. The critical importance of EVs and their biomolecular contents in breast cancer progression and metastasis are also discussed. Finally, we discuss the potential biomedical or clinical applications of these extracellular components, as well as how they impact treatment outcomes.

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IMPORTANCIA DEL MICROAMBIENTE TUMORAL EN LA PROGRESIÓN DEL CÁNCER DE MAMA

Revista ECIPeru ◽

10.33017/reveciperu2008.0005/ ◽

2019 ◽

pp. 1-7

Keyword(s):

Breast Cancer ◽

Endothelial Cells ◽

Tumor Microenvironment ◽

Cancer Progression ◽

Inflammatory Cells ◽

Cell Types ◽

Tumour Microenvironment ◽

Breast Cancer Progression ◽

Cáncer De Mama ◽

Cytokine Network

IMPORTANCIA DEL MICROAMBIENTE TUMORAL EN LA PROGRESIÓN DEL CÁNCER DE MAMA IMPORTANCE OF TUMOR MICROENVIRONMENT IN BREAST CANCER PROGRESSION Julio E. Valdivia-Silvaa, Eduardo García-Zepedab DOI: https://doi.org/10.33017/RevECIPeru2008.0005/ RESUMEN El microambiente tumoral, en el cáncer de mama y otros de estirpe epitelial, es un tejido complejo que comprende diferentes tipos celulares que incluyen las células tumorales, fibroblastos, células endoteliales, y leucocitos infiltrantes. Citocinas, quimiocinas, factores de crecimiento y proteasas son moléculas claves que controlan la comunicación autocrina y paracrina entre estas células individuales. Bajo algunas circunstancias, dichas moléculas pueden orquestar respuestas del hospedero contra el tumor, pero contradictoriamente existe evidencia que demuestra un rol paradójico que contribuye al crecimiento y progresión de la neoplasia además de inmunosupresión local. Adicionalmente, la progresión del cáncer de mama está asociada con una robusta neovascularización. Es claro que las células “normales” asociadas al tumor, como las inmunes, endoteliales y del estroma, conspiran con las cancerosas en promover este proceso. En ésta revisión enfocamos algunas de las acciones de citocinas inflamatorias y otras moléculas del microambiente tumoral sobre el comportamiento invasivo y metastásico del carcinoma mamario. Una mayor comprensión de estos tipos celulares y constituyentes moleculares del microambiente pueden ser usados en el diseño de terapias más efectivas contra el cáncer. Palabras clave: cáncer de mama, microambiente tumoral, metástasis, inflamación. ABSTRACT The epithelial tumour microenvironment is a complex tissue comprising variable numbers of tumour cells, fibroblasts, endothelial cells and infiltrating leucocytes. Cytokines, chemokines, growth factors, and proteases are key molecules controlling autocrine or paracrine communications within and between these individual cell types. Under some circumstances, endogenous cytokines may orchestrate host responses against the tumour, but there is increasing evidence that the cytokine network contributes to tumour growth, progression and host immuno-suppression. In addition, breast cancer progression is associated with and dependent upon robust neovascularization. It is becoming clear that tumour-associated „normal‟ cells, such as immune/inflammatory cells, endothelial cells and stromal cells, conspire with cancer cells in promoting this process. In this review we outline some of the actions of endogenous inflammatory cytokines and other molecules in tumor microenvironment over metastatic and invasive behavior of the breast carcinoma. A better understanding of these various cellular and molecular constituents of breast cancer microenvironment may be useful in designing more effective therapies. Keywords: breast cancer, tumour microenvironment, metastasis, inflammation.

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