scholarly journals Tumor microenvironment and breast cancer survival: combined effects of breast fat, M2 macrophages and hyaluronan create a dismal prognosis

2019 ◽  
Vol 179 (3) ◽  
pp. 565-575 ◽  
Author(s):  
Satu Tiainen ◽  
Amro Masarwah ◽  
Sanna Oikari ◽  
Kirsi Rilla ◽  
Kirsi Hämäläinen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Cancer Survival ◽  
Inflammatory Cells ◽  
Low Density ◽  
Chi Square ◽  
Dismal Prognosis ◽  
Cox's Model

Abstract Purpose Tumor microenvironment, including inflammatory cells, adipocytes and extracellular matrix constituents such as hyaluronan (HA), impacts on cancer progression. Systemic metabolism also influences tumor growth e.g. obesity and type 2 diabetes (T2D) are risk factors for breast cancer. Here, in 262 breast cancer cases, we explored the combined impacts on survival of M2-like tumor associated macrophages (TAMs), the abundance of breast fat visualized as low density in mammograms, and tumor HA, and their associations with T2D. Methods Mammographic densities were assessed visually from the diagnostic images and dichotomized into very low density (VLD, density ≤ 10%, “fatty breast”) and mixed density (MID, density > 10%). The amounts of TAMs (CD163+ and CD68+) and tumor HA were determined by immunohistochemistry. The data of T2D was collected from the patient records. Statistical differences between the parameters were calculated with Chi square or Mann–Whitney test and survival analyses with Cox’s model. Results A combination of fatty breasts (VLD), abundance of M2-like TAMs (CD163+) and tumor HA associated with poor survival, as survival was 88–89% in the absence of these factors but only 40–47% when all three factors were present (p < 0.001). Also, an association between T2D and fatty breasts was found (p < 0.01). Furthermore, tumors in fatty breasts contained more frequently high levels of M2-like TAMs than tumors in MID breasts (p = 0.01). Conclusions Our results demonstrate a dramatic effect of the tumor microenvironment on breast cancer progression. We hypothesize that T2D as well as obesity increase the fat content of the breasts, subsequently enhancing local pro-tumoral inflammation.

scholarly journals IMPORTANCIA DEL MICROAMBIENTE TUMORAL EN LA PROGRESIÓN DEL CÁNCER DE MAMA

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.

scholarly journals The Roles of Stroma-Derived Chemokine in Different Stages of Cancer Metastases

2020 ◽  
Vol 11 ◽  
Author(s):  
Shahid Hussain ◽  
Bo Peng ◽  
Mathew Cherian ◽  
Jonathan W. Song ◽  
Dinesh K. Ahirwar ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Tumor Development ◽  
Inflammatory Cells ◽  
Host Cells ◽  
Metastatic Niche ◽  
Cancer Pathogenesis ◽  
Cancer Metastases ◽  
Cellular Components

The intricate interplay between malignant cells and host cellular and non-cellular components play crucial role in different stages of tumor development, progression, and metastases. Tumor and stromal cells communicate to each other through receptors such as integrins and secretion of signaling molecules like growth factors, cytokines, chemokines and inflammatory mediators. Chemokines mediated signaling pathways have emerged as major mechanisms underlying multifaceted roles played by host cells during tumor progression. In response to tumor stimuli, host cells-derived chemokines further activates signaling cascades that support the ability of tumor cells to invade surrounding basement membrane and extra-cellular matrix. The host-derived chemokines act on endothelial cells to increase their permeability and facilitate tumor cells intravasation and extravasation. The tumor cells-host neutrophils interaction within the vasculature initiates chemokines driven recruitment of inflammatory cells that protects circulatory tumor cells from immune attack. Chemokines secreted by tumor cells and stromal immune and non-immune cells within the tumor microenvironment enter the circulation and are responsible for formation of a “pre-metastatic niche” like a “soil” in distant organs whereby circulating tumor cells “seed’ and colonize, leading to formation of metastatic foci. Given the importance of host derived chemokines in cancer progression and metastases several drugs like Mogamulizumab, Plerixafor, Repertaxin among others are part of ongoing clinical trial which target chemokines and their receptors against cancer pathogenesis. In this review, we focus on recent advances in understanding the complexity of chemokines network in tumor microenvironment, with an emphasis on chemokines secreted from host cells. We especially summarize the role of host-derived chemokines in different stages of metastases, including invasion, dissemination, migration into the vasculature, and seeding into the pre-metastatic niche. We finally provide a brief description of prospective drugs that target chemokines in different clinical trials against cancer.

scholarly journals The Complex Interaction between the Tumor Micro-Environment and Immune Checkpoints in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1205 ◽  
Author(s):  
Vanessa Barriga ◽  
Nyanbol Kuol ◽  
Kulmira Nurgali ◽  
Vasso Apostolopoulos
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Molecular Subtypes ◽  
Breast Cancer Subtype ◽  
Complex Interaction ◽  
Immune Checkpoints ◽  
Expression Studies ◽  
Cancer Subtype ◽  
Insight Into

The progression of breast cancer and its association with clinical outcome and treatment remain largely unexplored. Accumulating data has highlighted the interaction between cells of the immune system and the tumor microenvironment in cancer progression, and although studies have identified multiple facets of cancer progression within the development of the tumor microenvironment (TME) and its constituents, there is lack of research into the associations between breast cancer subtype and staging. Current literature has provided insight into the cells and pathways associated with breast cancer progression through expression analysis. However, there is lack of co-expression studies between immune pathways and cells of the TME that form pro-tumorigenic relationships contributing to immune-evasion. We focus on the immune checkpoint and TME elements that influence cancer progression, particularly studies in molecular subtypes of breast cancer.

scholarly journals Study of the tumor microenvironment during breast cancer progression

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Rahil Eftekhari ◽  
Rezvan Esmaeili ◽  
Reza Mirzaei ◽  
Katayoon Bidad ◽  
Stacy de Lima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Breast Cancer Progression

scholarly journals The Extracellular Matrix and Vesicles Modulate the Breast Tumor Microenvironment

2020 ◽  
Vol 7 (4) ◽  
pp. 124 ◽  
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.

scholarly journals miR-216a Acts as a Negative Regulator of Breast Cancer by Modulating Stemness Properties and Tumor Microenvironment

2020 ◽  
Vol 21 (7) ◽  
pp. 2313 ◽  
Author(s):  
Giuseppina Roscigno ◽  
Assunta Cirella ◽  
Alessandra Affinito ◽  
Cristina Quintavalle ◽  
Iolanda Scognamiglio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Negative Regulator ◽  
Mammosphere Formation ◽  
Incidence And Mortality ◽  
Cells Of The Microenvironment

Breast cancer is the most frequent malignancy in females in terms of both incidence and mortality. Underlying the high mortality rate is the presence of cancer stem cells, which divide indefinitely and are resistant to conventional chemotherapies, so causing tumor relapse. In the present study, we identify miR-216a-5p as a downregulated microRNA in breast cancer stem cells vs. the differentiated counterpart. We demonstrate that overexpression of miR-216a-5p impairs stemness markers, mammosphere formation, ALDH activity, and the level of Toll-like receptor 4 (TLR4), which plays a significant role in breast cancer progression and metastasis by leading to the release of pro-inflammatory molecules, such as interleukin 6 (IL-6). Indeed, miR-216a regulates the crosstalk between cancer cells and the cells of the microenvironment, in particular cancer-associated fibroblasts (CAFs), through regulation of the TLR4/IL6 pathway. Thus, miR-216a has an important role in the regulation of stem phenotype, decreasing stem-like properties and affecting the cross-talk between cancer cells and the tumor microenvironment.

Delta 32 mutation in CCR5 gene and its association with breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 17-17 ◽  
Author(s):  
Abid Azhar ◽  
Faria Fatima ◽  
Abdul Hameed ◽  
Saima Saleem
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Regulatory Region ◽  
Open Reading Frame ◽  
Receptor Protein ◽  
Breast Cancer Patients ◽  
Chi Square ◽  
Ccr5 Gene ◽  
Significant Positive Association ◽  
Reading Frame

17 Background: Chemokine C-C motif receptor type 5 (CCR5) is a chemokine receptor protein, which is present on the cell surface. Its potential role in cancer progression and metastasis has been implicated. Deletion mutation of 32 base pairs (bp) in the open reading frame of the CCR5 gene (CCR5Δ32) may lead to the malformation of the protein. This study aimed to examine the role of CCR5Δ32 mutation and its association with breast cancer. Methods: Blood samples of 500 breast cancer patients were included in the study. The samples were compared with age and sex matched healthy controls. Mutation of CCR5Δ32 was analyzed by sequence specific primers by polymerase chain reaction (PCR). They were examined on agarose gel electrophoresis. Statistical analyses were performed using software SPSS 17.0 (Chicago, IL., USA). The genotypic frequencies of patients and controls were tested by applying the chi‐square test. Results: Two types of CCR5 allelic mutations were found in the breast cancer samples. The mutation was of a 32 (bp) DNA fragment. Homozygous insertion (I/I) and heterozygous deletion (I/D) was found in the open reading frame of the regulatory region of the gene. The chi square analyses showed significant positive association between I/I and I/D allele in breast can patients with CCR5 delta 32 mutation (χ2 15.07, p < 0.01). Conclusions: This deletion in the promoter region of the CCR5 gene produces a non-functional receptor which may increase inflammation, leading to the enhanced progression of tumor.

scholarly journals Cytokine Secretions in Partial Breast Tumor Microenvironment With and Without Sulforaphane

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 274-274
Author(s):  
Courtney Merrick ◽  
Lauren Housley
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Treatment Options ◽  
Graduate Studies ◽  
Gm Csf ◽  
Funding Sources ◽  
Cytokine Levels ◽  
Vital Cell

Abstract Objectives Triple-negative breast cancer (TNBC) comprises 10–20% of breast cancer cases. It is particularly aggressive with limited and deleterious treatment options. Increasingly, research confirms that communication between cancer cells and neighboring macrophages promotes disease progression in part by secretion of cytokines that increase tumor cell proliferation, invasion, and metastasis. Sulforaphane (SFN) is a chemopreventive phytochemical found in cruciferous vegetables (broccoli) shown to alter cytokine secretion in macrophages and breast cancer cells grown in single culture. However, its effect in the tumor microenvironment remains unclear. This study aims to characterize cytokine profiles in media where TNBC cells and macrophages are grown in coculture with and without SFN treatment. We expect SFN to modify cytokine secretions in coculture media, suggesting SFN may disrupt vital cell-cell signaling needed for cancer progression. Methods TNBC cells (MDA-MB-231) were grown in Transwell plates with and without macrophages (THP-1 cells differentiated with PMA). Cell cultures (n = 3) were treated with either 15 μM SFN, DMSO (vehicle-control), or a non-treatment control. Cytokine levels were evaluated in media at 24 and 48 hours after treatment using BioPlex 2000 assay. Results Treatment with sulforaphane significantly reduced the levels of several targets in coculture including IL-1ra, IL-4, IL-5, IL-10, IL-12, IL-13, IL-15, IL-17, CCL2 (MCP-1), CCL11, CCL22, CCL26, CXCL12, IFN-y, G-CSF, GM-CSF, Eotaxin, and VEGF. Conversely, MIF was elevated following treatment. Effects were discovered at 24-hour and 48-hour time points. Conclusions We demonstrated that SFN altered the levels of numerous cellular signaling proteins in cancer cell-macrophage coculture, many of which are known to be involved with breast cancer progression. These results reveal mechanistic links underlying SFNs chemopreventive function and bolster SFNs potential as a treatment strategy for TNBC. Funding Sources Department of Nutrition and Food Science, CSU Chico; Graduate Studies, CSU Chico; CSUPERB: CSU Program for Education and Research in Biotechnology.

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