Macrophage inflammatory factors promote epithelial-mesenchymal transition in breast cancer

Bednarczyk, Robert B.; Tuli, Neha; Hanly, Elyse K.; Rahoma, Ghada Ben; Maniyar, Rachana; Mittelman, Abraham; Geliebter, Jan; Tiwari, Raj K.

doi:10.18632/oncotarget.24917

Cited by 33 publications

(30 citation statements)

References 52 publications

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“…These studies show that, upon interaction, CAFs induce an M2 phenotype in tumor infiltrating macrophages, and that macrophages can induce an EMT phenotype in resident fibroblasts through an intricate combination of IL‐6, stem cell factor 1, and TGF‐β signaling 123 . This protumorigenic reciprocity results in cancer cells that are highly mobile, invasive, and able evade immune mediated killing 124,125 . In this way, the enhanced fibrotic response following RT can preferentially intensify the immunosuppressive subpopulations of macrophages.…”

Section: Innate Immune Populationsmentioning

confidence: 92%

“…Through both direct binding and secreted factors, CAFs have been shown to preferentially recruit and support suppressive innate immune populations, reduce the frequency and effectiveness of natural killer cells, and impair the innate immune system's ability to initiate a T cell‐mediated antitumor response 63,128‐130 . These interactions result in an environment primed for disease progression 124,125,131 . CAF, cancer associated fibroblast; MDSC, myeolid derived suppressor cell [Color figure can be viewed at wileyonlinelibrary.com]…”

Section: Innate Immune Populationsmentioning

confidence: 99%

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The interplay between cancer associated fibroblasts and immune cells in the context of radiation therapy

Piper

Mueller

Karam

2020

Molecular Carcinogenesis

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Fibroblasts are a key component of the tumor microenvironment (TME) that can serve as a scaffold for tumor cell migration and augment the tumor's ability to withstand harsh conditions. When activated by external or endogenous stimuli, normal fibroblasts become cancer associated fibroblasts (CAFs), a heterogeneous group of stromal cells in the tumor that are phenotypically and epigenetically different from normal fibroblasts. Dynamic crosstalk between cancer cells, immune cells, and CAFs through chemokines and surface signaling makes the TME conducive to tumor growth. When activated, CAFs promote tumorigenesis and metastasis through several phenomena including regulation of tumor immunity, metabolic reprogramming of the TME, extracellular matrix remodeling and contraction, and induction of therapeutic resistance.Ionizing radiation (radiation theraphy [RT]) is a potent immunological stimulant that has been shown to increase cytotoxic Teff infiltration and IFN-I stimulated genes. RT, however, is unable to overcome the infiltration and activation of immunosuppressive cells which can contribute to tumor progression. Another paradox of RT is that, while very effective at killing cancer cells, it can contribute to the formation of CAFs. This review examines how the interplay between CAFs and immune cells during RT contributes to organ fibrosis, immunosuppression, and tumor growth. We focus on targeting mechanistic pathways of CAF formation as a potentially effective strategy not only for preventing organ fibrosis, but also in hampering tumor progression in response to RT. K E Y W O R D Scancer associated fibroblast, immune microenvironment, immunotherapy, radiation therapy

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Section: Innate Immune Populationsmentioning

confidence: 92%

Section: Innate Immune Populationsmentioning

confidence: 99%

The interplay between cancer associated fibroblasts and immune cells in the context of radiation therapy

Piper

Mueller

Karam

2020

Molecular Carcinogenesis

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“…The regulation of this phenomenon is complex and strictly dependent on other molecular parameters of the cancer cells. Bednarczyk et al noted a positive effect of increased matrix metallopeptidase 9 (MMP-9) expression on the migrative and invasive potential of adenocarcinoma cells induced by the M1 subpopulation [66].…”

Section: Tumor Associated Macrophagesmentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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“…Since we observed impaired vascularization, we hypothesize that, in our study, H 2 S promotes the differentiation of pro-inflammatory M1 macrophages [23]. These M1 macrophages could induce epithelial to mesenchymal transition (EMT) [24], which might explain the reduced number of endothelial cells in nude mice. In contrary, it seems that H 2 S in C57BL/6 mice has an anti-inflammatory effect, since a reduced number of macrophages and monocytes was found.…”

Section: Discussionmentioning

confidence: 60%

The Effect of a Fast-Releasing Hydrogen Sulfide Donor on Vascularization of Subcutaneous Scaffolds in Immunocompetent and Immunocompromised Mice

et al. 2020

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Islet transplantation into subcutaneous polymer scaffolds has shown to successfully induce normoglycemia in type 1 diabetes models. Vascularization of these scaffolds is imperative for optimal control of glucose levels. We studied the effect of the vascular stimulator hydrogen sulfide (H2S) on the degree of vascularization of a scaffold and the role of the immune system in this process. Scaffolds were subcutaneously implanted in immunocompetent C57BL/6 and immunocompromised nude mice. Mice received twice-daily intraperitoneal injections of the fast-releasing H2S donor sodium hydrosulfide (NaHS, 25 or 50 μmol/kg) or saline for 28 days. After 63 days the vascular network was analyzed by histology and gene expression. Here we showed that the vascularization of a subcutaneous scaffold in nude mice was significantly impaired by H2S treatment. Both the CD31 gene and protein expression were reduced in these scaffolds compared to the saline-treated controls. In C57BL/6 mice, the opposite was found, the vascularization of the scaffold was significantly increased by H2S. The mRNA expression of the angiogenesis marker CD105 was significantly increased compared to the controls as well as the number of CD31 positive blood vessels. In conclusion, the immune system plays an important role in the H2S mediated effect on vascularization of subcutaneous scaffolds.

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Macrophage inflammatory factors promote epithelial-mesenchymal transition in breast cancer

Cited by 33 publications

References 52 publications

The interplay between cancer associated fibroblasts and immune cells in the context of radiation therapy

The interplay between cancer associated fibroblasts and immune cells in the context of radiation therapy

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

The Effect of a Fast-Releasing Hydrogen Sulfide Donor on Vascularization of Subcutaneous Scaffolds in Immunocompetent and Immunocompromised Mice

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