The role of immune semaphorins in cancer progression

Eißler, Nina; Rolny, Charlotte

doi:10.1016/j.yexcr.2013.04.016

Cited by 8 publications

(13 citation statements)

References 65 publications

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“…In cancer context, SEMA3A plays pleiotropic activities controlling tumor cells, tumor vessels and infiltrating inflammatory cells. Several data support a vessel-regulating and tumor suppressor function of SEMA3A, but there are discordant findings [25,26]. Indeed, SEMA3A expression was found to decrease in advanced stage tumors, but other studies correlated high tumor levels of SEMA3A with poor outcome [27,28].…”

Section: Semaphorin 3amentioning

confidence: 99%

Semaphorin Signaling in Cancer-Associated Inflammation

Franzolin

Tamagnone

2019

IJMS

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The inflammatory and immune response elicited by the growth of cancer cells is a major element conditioning the tumor microenvironment, impinging on disease progression and patients’ prognosis. Semaphorin receptors are widely expressed in inflammatory cells, and their ligands are provided by tumor cells, featuring an intense signaling cross-talk at local and systemic levels. Moreover, diverse semaphorins control both cells of the innate and the antigen-specific immunity. Notably, semaphorin signals acting as inhibitors of anti-cancer immune response are often dysregulated in human tumors, and may represent potential therapeutic targets. In this mini-review, we provide a survey of the best known semaphorin regulators of inflammatory and immune cells, and discuss their functional impact in the tumor microenvironment.

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Section: Semaphorin 3amentioning

confidence: 99%

Semaphorin Signaling in Cancer-Associated Inflammation

Franzolin

Tamagnone

2019

IJMS

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“…SEMA3A binds to its receptor, neuropilin 1 (NP1), which in turn leads to activation of the Plexin A family (Plexin A1-4) signaling complex, which transmits SEMA3A-mediated downstream signals regulating cell survival, proliferation, and migration (10,11). We and others have shown that SEMA3A restricts tumor growth mainly by hampering tumor angiogenesis [reviewed in (12)]. However, the role of SEMA3A in tumor immunity remains poorly defined.…”

Section: Introductionmentioning

confidence: 99%

Guidance Molecule SEMA3A Restricts Tumor Growth by Differentially Regulating the Proliferation of Tumor-Associated Macrophages

et al. 2016

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Accumulation of tumor-associated macrophages (TAM) correlates with malignant progression, immune suppression, and poor prognosis. In this study, we defined a critical role for the cellsurface guidance molecule SEMA3A in differential proliferative control of TAMs. Tumor cell-derived SEMA3A restricted the proliferation of protumoral M2 macrophages but increased the proliferation of antitumoral M1, acting through the SEMA3A receptor neuropilin 1. Expansion of M1 macrophages in vivo enhanced the recruitment and activation of natural killer (NK) cells and cytotoxic CD8þ T cells to tumors, inhibiting their growth. In human breast cancer specimens, we found that immunohistochemical levels of SEMA3A correlated with the expression of genes characteristic of M1 macrophages, CD8 þ T cells, and NK cells, while inversely correlating with established characters of malignancy. In summary, our results illuminate a mechanism whereby the TAM phenotype is controlled and identify the cellsurface molecule SEMA3A as a candidate for therapeutic targeting.Cancer Res; 76(11); 3166-78. Ó2016 AACR.

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“…Moreover, some semaphorins may show both protumoral and antitumoral activities in a tumor-dependent manner (Neufeld et al, 2012). In addition, immune semaphorins, affecting both innate and adaptive arms of immunity, could represent a possible link in mediating the molecular cross-talk between tumor cells and multiple stromal cells (Tamagnone, 2012;Eissler and Rolny, 2013;Rehman and Tamagnone, 2013). Although tumor-suppressive semaphorins and plexins are often downregulated in cancers, the expression of tumor-promoting protein subsets generally increases, thus highlighting the importance of their delicate balance in maintaining tissue homeostasis.…”

Section: Semaphorins and Plexins In Cancer Műzes And Sipos 471mentioning

confidence: 99%

Relation of immune semaphorin/plexin signaling to carcinogenesis

Műzes

Sípos

2014

European Journal of Cancer Prevention

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Semaphorins and plexins represent a highly conserved group of proteins that have recently been found to exert widespread regulatory functions outside the nervous system, including angiogenesis and immune regulation. Furthermore, these molecules are definitely implicated in the etiology of carcinogenesis and immune disorders. Their expression patterns and levels are deregulated in cancer cells and in cells of the tumor milieu. During the multistep development of cancer, its characteristic features include sustained tumor cell proliferation, resistance to cell death, limitless replicative capacity, activation of angiogenesis along with invasion and metastatic spread, cancer-related smoldering inflammation, and evasion of antitumor immune responses. The diversity of the semaphorin/plexin complexes and, thus, the multiple stimulated molecular interactions allow varied and diverse cell signaling events. The elicited transduction pathways might be involved in modifying the intricate mechanisms of tumorigenesis. Indeed, these pleiotropic signals may influence not only the intrinsic properties of cancer cells but they could also represent a possible link in mediating the cross-talk between tumor cells and the surrounding multiple stromal cells. In tumorigenesis, however, a dual role of different semaphorins is proposed, as some of them may elicit tumor regression, whereas others definitely promote cancer cell survival and progression. The current antitumoral or prosurvival responsiveness to semaphorins is mainly cell context dependent; nevertheless, their precise relation to cancer networks has not yet been fully elucidated. Here, we survey the many faces of a subset of the large semaphorin family, termed immune semaphorins, in carcinogenesis.

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The role of immune semaphorins in cancer progression

Cited by 8 publications

References 65 publications

Semaphorin Signaling in Cancer-Associated Inflammation

Semaphorin Signaling in Cancer-Associated Inflammation

Guidance Molecule SEMA3A Restricts Tumor Growth by Differentially Regulating the Proliferation of Tumor-Associated Macrophages

Relation of immune semaphorin/plexin signaling to carcinogenesis

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