IL-6 roles – Molecular pathway and clinical implication in pancreatic cancer – A systemic review

Pop, Victor I.; Seicean, Andrada; Lupan, Iulia; Samaşcă, Gabriel; Burz, Claudia

doi:10.1016/j.imlet.2016.11.010

Cited by 67 publications

(57 citation statements)

References 55 publications

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“…IL-6 is a multipotent cytokine secreted by various immune cells, such as monocytes, macrophages, fibroblasts and tumour cells [55]. Additionally, the IL-6 receptor (IL-6R) system and signal transduction mechanism has importance in immune regulation and inflammation [56].…”

Section: Il-6mentioning

confidence: 99%

Methamphetamine and its immune-modulating effects

et al. 2019

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Methamphetamine (METH, or ice) use is a global burden, which continues to pervade and plague contemporary society with estimates of up to 35 million users worldwide. METH is a psychotropic compound which acts on the central nervous system, and, in chronic doses, can induce psychotic behavior from its highly addictive nature. METH harbours the capacity to cause modulation of immune cells, enabling the drug to have lasting, long-term effects which may manifest into neuropsychiatric disorders, as well as leading to increased susceptibility to communicable diseases, such as HIV. In addition, changes to the cytokine balance have been associated with blood brain barrier compromise, resulting to alterations to brain plasticity, creating lasting neurotoxicity. Furthermore, immune-related signaling pathways are key to further evaluating how METH impacts the host immunity through these neurological and peripheral modifications. Layering this knowledge with current data on inflammatory responses can help facilitate a better understanding of how the host adaptive and innate immunity responds to METH, how this can activate premature-ageing processes and how METH exacerbates disturbances leading to non-communicable age-related diseases, including cardiovascular disease, stroke, depression and dementia.

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Section: Il-6mentioning

confidence: 99%

Methamphetamine and its immune-modulating effects

et al. 2019

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“…Once the tyrosine is phosphorylated, two STAT3 monomers form dimers through reciprocal phosphotyrosine-SH2 interactions, translocate to the nucleus, where they bind to STAT3-specific DNA-response elements of target genes, and induce gene transcription (31). Thus, IL-6 induces the activation of its downstream cascade the JAK2/STAT3 signaling pathway, resulting in tumorigenesis by regulating cell cycle progression, angiogenesis and tumor cell evasion of the immune system (32)(33)(34). Evidence reveals an important role of IL-6/JAK2/STAT3 signaling in the development of pancreatic cancer (31).…”

Section: Discusssionmentioning

confidence: 99%

Tyrphostin B42 attenuates trichostatin A-mediated resistance in pancreatic cancer cells by antagonizing IL-6/JAK2/STAT3 signaling

Zhang

Hong

et al. 2018

Oncol Rep

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Drug-resistance is the key reason for the ineffectiveness of chemotherapy in pancreatic cancer. Thus, it is very important to explore the molecular mechanisms of drug‑resistance and the methods of effective intervention. In the present study, we investigated the effect of tyrphostin B42, also called AG490, on histone deacetylase (HDAC) inhibitor trichostatin A (TSA)‑induced resistance in pancreatic cancer cells (PCCs). Evidence from phase contrast microscope revealed that TSA‑resistant cells (PANC‑1‑TSA) had higher proliferative activity than non‑resistant cells (PANC‑1). This over‑proliferative activity induced by TSA may be associated with abnormal activation of JAK2/STAT3 signaling, which can be strengthened by interleukin‑6 (IL‑6), a STAT3‑upstream inducer, resulting in enhanced expression of STAT3-downstream target genes including c‑Myc, c‑Src, HIF‑1α, and CCND1. In addition, increased expression of Bcl‑2 mRNA and decreased expression of Bax mRNA in PANC‑1‑TSA cells indicated that TSA induced the inhibition of mitochondrial-dependent apoptosis in PCCs. Tyrphostin B42 treatment evidently antagonized the activation of IL‑6/JAK2/STAT3 in a dose‑dependent manner. As a result, tyrphostin B42 inhibited the over‑proliferative activity of PANC‑1‑TSA cells, and downregulated the expression of IL‑6/JAK2/STAT3‑downstream target genes. Moreover, tyrphostin B42 induced the apoptosis of PCCs by regulating the expression of mitochondrial‑related genes. Therefore, these findings demonstrated that tyrphostin B42 attenuated TSA‑mediated resistance in PCCs by antagonizing the IL‑6/JAK2/STAT3 signaling.

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“…Many previous studies have shown that higher serum levels of proinflammatory cytokines (e.g. IL-6 and TNF␣) correlate with advanced metastatic stages and poor survival in various types of cancer (34). These cytokines enhance various cell activities, including proliferation, invasion, angiogenesis, and metastasis (15,35).…”

Section: Galectin-3-cd146 Interaction Induces Cytokine Secretionmentioning

confidence: 99%

Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells

Colomb

Wang

Simpson

et al. 2017

Journal of Biological Chemistry

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The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model. This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines. Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion. Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells. CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3. Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling. siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells. Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines. We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.Galectin-3 is a galactoside-binding protein that is expressed by many types of human cells. Overexpression of galectin-3 commonly occurs in most types of cancer (1, 2) and is increasingly recognized to influence cancer cell-cell and cancer-microenvironment communications and contributes to cancer development, progression, and metastasis as a result of galectin-3 interaction with various galactose-terminated glycans carried on the cell surface and in the extracellular matrix (2).Earlier studies by us as well as by other groups have revealed that the concentration of circulating galectin-3 is markedly increased, up to 30-fold, in the bloodstream of cancer patients, including those with colorectal, breast, lung, bladder, pancreatic, and head and neck cancers and melanoma (2-8). Patients with metastatic disease tend to have higher concentrations of circulating galectin-3 than those with only localized tumors (3). Our recent study has revealed that increased circulating galectin-3 is an important promoter of blood-borne metastasis in a mouse model (9). This effect of galectin-3 is shown to be partly attributed to galectin-3 interaction with the oncofetal Thomsen-Friedenreich (galactose␤1,3-N-acetyl-galactosamine ␣-, TF) disaccharide expressed on the cancer-associated transmembr...

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IL-6 roles – Molecular pathway and clinical implication in pancreatic cancer – A systemic review

Cited by 67 publications

References 55 publications

Methamphetamine and its immune-modulating effects

Methamphetamine and its immune-modulating effects

Tyrphostin B42 attenuates trichostatin A-mediated resistance in pancreatic cancer cells by antagonizing IL-6/JAK2/STAT3 signaling

Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells

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