Host microenvironment in breast cancer development: Inflammatory cells, cytokines and chemokines in breast cancer progression: reciprocal tumor–microenvironment interactions

Evidence is increasing on the crucial role of the extracellular matrix (ECM) in breast cancer progression, invasion and metastasis with almost all mortality cases owing to metastasis. The epithelial-mesenchymal transition is the first signal of metastasis involving different transcription factors such as Snail, TWIST, and ZEB1. ECM remodeling is a major event promoting cancer invasion and metastasis; where matrix metalloproteinases (MMPs) such as MMP-2, -9, -11, and -14 play vital roles degrading the matrix proteins for cancer spread. The β-D mannuronic acid (MMP inhibitor) has anti-metastatic properties through inhibition of MMP-2, and -9 and could be a potential therapeutic agent. Besides the MMPs, the enzymes such as LOXL2, LOXL4, procollagen lysyl hydroxylase-2, and heparanase also regulate breast cancer progression. The important ECM proteins like integrins (b1-, b5-, and b6- integrins), ECM1 protein, and Hic-5 protein are also actively involved in breast cancer development. The stromal cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and adipocytes also contribute in tumor development through different processes. The TAMs become proangiogenic through secretion of VEGF-A and building vessel network for nourishment and invasion of the tumor mass. The latest developments of ECM involvement in breast cancer progression has been discussed in this review and this study will help researchers in designing future work on breast cancer pathogenesis and developing therapy targeted to the ECM components.

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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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Using the MCF10A/MCF10CA1a Breast Cancer Progression Cell Line Model to Investigate the Effect of Active, Mutant Forms of EGFR in Breast Cancer Development and Treatment Using Gefitinib

PLoS ONE ◽

10.1371/journal.pone.0125232 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0125232 ◽

Cited By ~ 16

Author(s):

Darrell C. Bessette ◽

Erik Tilch ◽

Tatjana Seidens ◽

Michael C. J. Quinn ◽

Adrian P. Wiegmans ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cancer Progression ◽

Breast Cancer Progression ◽

Cancer Development ◽

Line Model ◽

Breast Cancer Development ◽

Cell Line Model ◽

Mutant Forms

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Role of extracellular matrix in breast cancer development: a brief update

F1000Research ◽

10.12688/f1000research.14133.1 ◽

2018 ◽

Vol 7 ◽

pp. 274 ◽

Cited By ~ 1

Author(s):

Manoj Kumar Jena ◽

Jagadeesh Janjanam

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Cancer Progression ◽

Breast Cancer Progression ◽

Cancer Development ◽

Invasion And Metastasis ◽

Mesenchymal Transition ◽

Breast Cancer Development ◽

Cancer Pathogenesis

Evidence is increasing on the crucial role of the extracellular matrix (ECM) in breast cancer progression, invasion and metastasis with almost all mortality cases owing to metastasis. The epithelial-mesenchymal transition is the first signal of metastasis involving different transcription factors such as Snail, TWIST, and ZEB1. ECM remodeling is a major event promoting cancer invasion and metastasis; where matrix metalloproteinases (MMPs) such as MMP-2, -9, -11, and -14 play vital roles degrading the matrix proteins for cancer spread. The β-D mannuronic acid (MMP inhibitor) has anti-metastatic properties through inhibition of MMP-2, and -9 and could be a potential therapeutic agent. Besides the MMPs, the enzymes such as LOXL2, LOXL4, procollagen lysyl hydroxylase-2, and heparanase also regulate breast cancer progression. The important ECM proteins like integrins (b1-, b5-, and b6- integrins), ECM1 protein, and Hic-5 protein are also actively involved in breast cancer development. The stromal cells such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and adipocytes also contribute in tumor development through different processes. The TAMs become proangiogenic through secretion of VEGF-A and building vessel network for nourishment and invasion of the tumor mass. The latest developments of ECM involvement in breast cancer progression has been discussed in this review and this study will help researchers in designing future work on breast cancer pathogenesis and developing therapy targeted to the ECM components.

Download Full-text

Study of the tumor microenvironment during breast cancer progression

Cancer Cell International ◽

10.1186/s12935-017-0492-9 ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 9

Author(s):

Rahil Eftekhari ◽

Rezvan Esmaeili ◽

Reza Mirzaei ◽

Katayoon Bidad ◽

Stacy de Lima ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

Cancer Progression ◽

Breast Cancer Progression

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Abstract 3250: B cell-produced IL-27 up-regulates PD-L1 expression in the tumor microenvironment to promote breast cancer development

10.1158/1538-7445.sabcs18-3250 ◽

2019 ◽

Author(s):

Hui Yan ◽

Suryavathi Viswanadhapalli ◽

Daniel Chupp ◽

Maria Fernandez ◽

Shuai Wu ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

B Cell ◽

Cancer Development ◽

Breast Cancer Development ◽

Promote Breast Cancer

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The Extracellular Matrix and Vesicles Modulate the Breast Tumor Microenvironment

Bioengineering ◽

10.3390/bioengineering7040124 ◽

2020 ◽

Vol 7 (4) ◽

pp. 124 ◽

Cited By ~ 1

Author(s):

Jun Yang ◽

Gokhan Bahcecioglu ◽

Pinar Zorlutuna

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Tumor Microenvironment ◽

Cancer Progression ◽

Signaling Molecules ◽

Clinical Applications ◽

Breast Cancer Progression ◽

Multiple Roles ◽

Biophysical Properties ◽

The Impact

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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The Effects of Adipocytes on the Regulation of Breast Cancer in the Tumor Microenvironment: An Update

Cells ◽

10.3390/cells8080857 ◽

2019 ◽

Vol 8 (8) ◽

pp. 857 ◽

Cited By ~ 16

Author(s):

Chu ◽

Phuong ◽

Tien ◽

Tran ◽

Nguyen ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

Tumor Therapy ◽

Cancer Development ◽

Systemic Review ◽

Breast Cancer Development ◽

Invasion And Migration ◽

Metabolic Substrates

Obesity is a global pandemic and it is well evident that obesity is associated with the development of many disorders including many cancer types. Breast cancer is one of that associated with a high mortality rate. Adipocytes, a major cellular component in adipose tissue, are dysfunctional during obesity and also known to promote breast cancer development both in vitro and in vivo. Dysfunctional adipocytes can release metabolic substrates, adipokines, and cytokines, which promote proliferation, progression, invasion, and migration of breast cancer cells. The secretion of adipocytes can alter gene expression profile, induce inflammation and hypoxia, as well as inhibit apoptosis. It is known that excessive free fatty acids, cholesterol, triglycerides, hormones, leptin, interleukins, and chemokines upregulate breast cancer development. Interestingly, adiponectin is the only adipokine that has anti-tumor properties. Moreover, adipocytes are also related to chemotherapeutic resistance, resulting in the poorer outcome of treatment and advanced stages in breast cancer. Evaluation of the adipocyte secretion levels in the circulation can be useful for prognosis and evaluation of the effectiveness of cancer therapy in the patients. Therefore, understanding about functions of adipocytes as well as obesity in breast cancer may reveal novel targets that support the development of new anti-tumor therapy. In this systemic review, we summarize and update the effects of secreted factors by adipocytes on the regulation of breast cancer in the tumor microenvironment.

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