DNA damage induces the IL-6/STAT3 signaling pathway, which has anti-senescence and growth-promoting functions in human tumors

Yun, Un Jung; Park, Sang Eun; Jo, Yong Sam; Kim, Jungbin; Shin, Deug Y.

doi:10.1016/j.canlet.2012.04.003

Cited by 59 publications

(46 citation statements)

References 30 publications

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“…IL-6-STAT3 signaling is involved in tumor growth and metastasis of human hepatocellular carcinoma (Yang et al, 2013). In addition, DNA damage induces the IL-6-STAT3 signaling pathway, which has growth-promoting functions in human tumors (Yun et al, 2012). Based on these previous findings and our results, we hypothesize that Tim-3 might facilitate tumor metastasis through the IL-6-STAT3 pathway.…”

Section: Discussionsupporting

confidence: 77%

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Prognostic Value of T Cell Immunoglobulin Mucin-3 in Prostate Cancer

Piao¹,

Li²,

Zhu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 77%

“…In vitro, Tim-3 can activate the interleukin-6 (IL-6)-STAT3 pathway. According to published data (Yun et al, 2012;Yang et al, 2013). IL-6-STAT3 pathway plays an important role in tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of T Cell Immunoglobulin Mucin-3 in Prostate Cancer

Piao¹,

Li²,

Zhu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…It is now known that it is a pleiotropic cytokine with a key role in a multitude of processes such as regulation of the immune response, hematopoiesis, inflammation, cell survival, apoptosis, cell proliferation and oncogenesis [91,92] . The action of IL-6 is mediated by its binding with a membrane IL-6 receptor (mIL-6R) and gp130 as gp130 interacts with the JAK-STAT system [91] .…”

Section: Il-6mentioning

confidence: 99%

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Kyurkchiev

Bochev

Ivanova‐Todorova

et al. 2014

WJSC

526

392

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According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells (MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system. © 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Mesenchymal stem cells; Immunomodulation; Cytokines; Chemokines; Dendritic cells Core tip: Autoimmune diseases affect approximately 5% of the human population, leading to serious disability and effective methods to treat these diseases are still not perfect. Mesenchymal stem cells (MSCs) are assumed to be promising agents, both for regenerative medicine and cell therapy for autoimmune disorders. Under the influence of some factors, mesenchymal stem cells secrete cytokines which induce suppression of the immune response. Studies on the secreted cytokines and the precise mechanisms involved in these suppressive mechanisms would create possibilities for efficient application of MSCs as a therapeutic means for treatment of autoimmune diseases.Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, REVIEWSubmit a

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“…It was suggested that the nature of the IL-6 target cell decides whether IL-6 acts as tumor suppressor or promoter (Kuilman et al 2008, Yun et al 2012. The genetic makeup of the IL-6 target cell, whether normal or transformed, could contribute to specifying the biological response to IL-6.…”

Section: R244mentioning

confidence: 99%

Programmed cell senescence: role of IL-6 in the pituitary

Sapochnik

Fuertes

Arzt

2017

Journal of Molecular Endocrinology

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IL-6 is a pleiotropic cytokine with multiple pathophysiological functions. As a key factor of the senescence secretome, it can not only promote tumorigenesis and cell proliferation but also exert tumor suppressive functions, depending on the cellular context. IL-6, as do other cytokines, plays important roles in the function, growth and neuroendocrine responses of the anterior pituitary gland. The multiple actions of IL-6 on normal and adenomatous pituitary function, cell proliferation, angiogenesis and extracellular matrix remodeling indicate its importance in the regulation of the anterior pituitary. Pituitary tumors are mostly benign adenomas with low mitotic index and rarely became malignant. Premature senescence occurs in slow-growing benign tumors, like pituitary adenomas. The dual role of IL-6 in senescence and tumorigenesis is well represented in pituitary tumor development, as it has been demonstrated that effects of paracrine IL-6 may allow initial pituitary cell growth, whereas autocrine IL-6 in the same tumor triggers senescence and restrains aggressive growth and malignant transformation. IL-6 is instrumental in promotion and maintenance of the senescence program in pituitary adenomas.

show abstract

DNA damage induces the IL-6/STAT3 signaling pathway, which has anti-senescence and growth-promoting functions in human tumors

Cited by 59 publications

References 30 publications

Prognostic Value of T Cell Immunoglobulin Mucin-3 in Prostate Cancer

Prognostic Value of T Cell Immunoglobulin Mucin-3 in Prostate Cancer

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Programmed cell senescence: role of IL-6 in the pituitary

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