Contribution of adrenergic mechanisms for the stress‐induced breast cancer carcinogenesis

Silva, Dany; Quintas, Clara; Gonçalves, Jorge; Fresco, Paula

doi:10.1002/jcp.30707

Cited by 17 publications

(10 citation statements)

References 173 publications

(462 reference statements)

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“…Adrenergic stress is one of several culprits behind immunosuppression inside the TME, and has evolved recently as an important regulator of inflammation, immunity, and cancer [ 96 ]. Chronic release of NA inside the TME influences tumor growth by impeding immune responses, as is evident in preclinical models of some cancers [ 10 , 97 ]. β2-AR, among adrenergic receptors, is the most studied receptor for its immunosuppressive function in T lymphocytes.…”

Section: Perspective For Car-t Cell Therapymentioning

confidence: 99%

“…β2-Adrenergic receptors can modulate the functions of various immune cells as the corresponding receptors are displayed on the surface of T cells, natural killer (NK) cells, and dendritic cells (DCs) [ 7 , 8 ]. The ligand for β2-AR is released inside the tumor microenvironment (TME) and leads to inhibitory signaling in T lymphocytes [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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β2-Adrenergic Receptor Mediated Inhibition of T Cell Function and Its Implications for CAR-T Cell Therapy

Farooq

Ajmal

Hui

et al. 2023

IJMS

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The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of the tumor microenvironment, nor-adrenaline (NA) is poured in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surfaces of cancer and immune cells and are often involved in the activation of pro-tumoral signaling pathways. Beta2-adrenergic receptors (β2-ARs) are an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate regulatory immune cells and inhibit effector immune cells. Blocking β2-AR increases activation, proliferation, and cytokine release of T lymphocytes. Moreover, β2-AR deficiency during metabolic reprogramming of T cells increases mitochondrial membrane potential and biogenesis. In the view of the available research data, the immunosuppressive role of β2-AR in T cells presents it as a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged the contemporary knowledge about adrenergic-stress-mediated β2-AR activation on T lymphocytes inside tumor milieu.

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Section: Perspective For Car-t Cell Therapymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

β2-Adrenergic Receptor Mediated Inhibition of T Cell Function and Its Implications for CAR-T Cell Therapy

Farooq

Ajmal

Hui

et al. 2023

IJMS

View full text Add to dashboard Cite

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“…Adrenergic signaling may promote neoplastic transformation of breast epithelial cells in the initiation phase; however, it may also favor the metastatic potential of breast cancer cells during cancer progression. Although the presence of mesenchymal cells is essential for the induction of tumorigenesis, adrenergic signaling not only affects directly mesenchymal and tumor cells but also the function and activity of other cell types in the TME, where macrophages, fibroblasts, and fat cells can take on a kind of protumor phenotype [ 34 ]. Based on a previous BRCA cell line study, amongst all AR types, ß2ARs seem to be the most relevant receptors involved in the development of BRCA metastasis.…”

Section: Review Of the Literaturementioning

confidence: 99%

ß-Adrenoreceptors in Human Cancers

Kraboth

Kálmán

2023

IJMS

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Cancer is the leading cause of death and represents a significant economic burden worldwide. The numbers are constantly growing as a result of increasing life expectancy, toxic environmental factors, and adoption of Western lifestyle. Among lifestyle factors, stress and the related signaling pathways have recently been implicated in the development of tumors. Here we present some epidemiological and preclinical data concerning stress-related activation of the ß-adrenoreceptors (ß-ARs), which contributes to the formation, sequential transformation, and migration of different tumor cell types. We focused our survey on research results for breast and lung cancer, melanoma, and gliomas published in the past five years. Based on the converging evidence, we present a conceptual framework of how cancer cells hijack a physiological mechanism involving ß-ARs toward a positive modulation of their own survival. In addition, we also highlight the potential contribution of ß-AR activation to tumorigenesis and metastasis formation. Finally, we outline the antitumor effects of targeting the ß-adrenergic signaling pathways, methods for which primarily include repurposed ß-blocker drugs. However, we also call attention to the emerging (though as yet largely explorative) method of chemogenetics, which has a great potential in suppressing tumor growth either by selectively modulating neuronal cell groups involved in stress responses affecting cancer cells or by directly manipulating specific (e.g., the ß-AR) receptors on a tumor and its microenvironment.

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“…In an orthotopic ovarian cancer mouse model it has been demonstrated that depletion of TAMs by using clodronate liposomes attenuated tumor growth through the inhibition of angiogenesis [ 75 ]. Moreover, TAMs also secrete other proangiogenic growth factors such as EGF, PDGF, FGF2, TGF-β, TNF-α, semaphorin 4D, adrenomedullin, thymidine phosphorylase, IL-6, IL-1 β , IL-8, CCL2, CXCL8, and CXCL12 which promote neovascularization at several steps including supporting the proliferation of endothelial cells (eCs), as well as inducing sprouting, tube formation, and maturation of new blood vessels [ 4 , 11 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. In addition, there are several enzymes that are often expressed by TAMs including MMP-2, MMP-7, MMP-9, MMP-12, and cyclooxygenase-2 that can have a profound influence on tumor angiogenesis [ 83 ].…”

Section: Pro-tumorigenic Roles Of Tamsmentioning

confidence: 99%

Macrophages as a Potential Immunotherapeutic Target in Solid Cancers

et al. 2022

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The revolution in cancer immunotherapy over the last few decades has resulted in a paradigm shift in the clinical care of cancer. Most of the cancer immunotherapeutic regimens approved so far have relied on modulating the adaptive immune system. In recent years, strategies and approaches targeting the components of innate immunity have become widely recognized for their efficacy in targeting solid cancers. Macrophages are effector cells of the innate immune system, which can play a crucial role in the generation of anti-tumor immunity through their ability to phagocytose cancer cells and present tumor antigens to the cells of adaptive immunity. However, the macrophages that are recruited to the tumor microenvironment predominantly play pro-tumorigenic roles. Several strategies targeting pro-tumorigenic functions and harnessing the anti-tumorigenic properties of macrophages have shown promising results in preclinical studies, and a few of them have also advanced to clinical trials. In this review, we present a comprehensive overview of the pathobiology of TAMs and their role in the progression of solid malignancies. We discuss various mechanisms through which TAMs promote tumor progression, such as inflammation, genomic instability, tumor growth, cancer stem cell formation, angiogenesis, EMT and metastasis, tissue remodeling, and immunosuppression, etc. In addition, we also discuss potential therapeutic strategies for targeting TAMs and explore how macrophages can be used as a tool for next-generation immunotherapy for the treatment of solid malignancies.

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Contribution of adrenergic mechanisms for the stress‐induced breast cancer carcinogenesis

Cited by 17 publications

References 173 publications

β2-Adrenergic Receptor Mediated Inhibition of T Cell Function and Its Implications for CAR-T Cell Therapy

β2-Adrenergic Receptor Mediated Inhibition of T Cell Function and Its Implications for CAR-T Cell Therapy

ß-Adrenoreceptors in Human Cancers

Macrophages as a Potential Immunotherapeutic Target in Solid Cancers

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