IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia

Abstract

OBJECTIVES: We investigated the changes in the IL-6 and STAT3 expression levels in cachectic and noncachectic patients with gastric, lung and breast cancer and evaluated the association between IL-6 and STAT3 levels and cancer types in terms of cachexia condition. BACKGROUND: Cancer-associated cachexia, observed in nearly 50-80 % of cancer patients, has drawn attention in advanced patients. IL-6/JAK/STAT pathway plays an essential role in the progression of cancer cachexia through the regulation of the infl ammatory response. METHODS: This study consisted of 48 gastric, breast and lung cancer patients (18 cachectic and 30 noncachectic) and healthy individuals. Total RNA isolation and cDNA synthesis was performed after the collection of blood samples. IL-6 and STAT3 expression levels were analyzed by RT-PCR analysis. RESULTS: Our fi ndings demonstrated that IL-6 mRNA levels considerably increased 19.89 ± 8.25, 5.18 ± 2.81 and 15.33±9.54-fold in gastric, lung and breast cancer patients with cachexia, respectively. Additionally, a 16.67±7.13, 14.21 ± 11.72 and 8.85 ± 3.89-fold increase in the STAT3 expression level was detected in cachectic gastric, lung and breast cancer patients, respectively (p < 0.01). CONCLUSION: STAT3 may be considered as a therapeutic target for cachectic patients with gastric, lung and breast cancer. Furthermore, IL-6 mediates STAT3 activation in cachectic gastric and breast cancer patients (Tab. 5, Fig. 2, Ref. 62).

Molecular mechanisms of cancer cachexia‑induced muscle atrophy (Review)

“…IL-6. Numerous proinflammatory factors have been discovered to serve important roles in the muscle atrophy caused by cancer cachexia (13,29,60,61). il-6 is produced by macrophages (62) and fibroblasts (63) and was also found to be secreted by tumor cells (64).…”

“…clinical studies have also revealed that compared with healthy controls, patients with non-small cell lc (nSclc) with cachexia had smaller muscle fiber cross-sectional areas and significantly increased plasma il-6 levels (68). The il-6/Janus kinase (JaK)/STaT3 signaling pathway was discovered to have an essential role in the progression of cancer cachexia by regulating the inflammatory response (13,60). Pin et al (61) intraperitoneally injected eS-2 human ovarian cancer cells into nod-Scidγ mice to establish a cancer cachexia model; the experimental studies revealed significantly upregulated IL-6 and phosphorylated STaT3 levels in the plasma and ascites of model mice compared with control mice.…”

“…STaT3 may be considered as a therapeutic target for patients with cachexia with gastric, lung and breast cancer. For example, a previous study identified that IL-6 mediated STAT3 activation in cachectic patients with gastric and breast cancer (60). STaT3 can also induce the iκB kinase (iKK)/nF-κB signaling pathway, which was discovered to mediate apoptosis and muscle atrophy (92).…”

Impact of the anatomical location and the number of metastatic lymph nodes on gastric cancer patient´s survival

“…N-ratio staging system -the staging system based on the metastatic lymph node ratio between metastatic and examined lymph nodes (N-ratio) in gastric cancer patients (2,5,7,8,10,11).…”

Polymorphism of The Regulatory Region of the ITGAM Gene (-323G>A) as a Novel Predictor of a Poor Nutritional Status in Head and Neck Cancer Patients Subjected to Intensity-Modulated Radiation Therapy

“…The resulting cytokines participate in the pathways activating the processes related to the destruction of muscle fibers as well as the reduction of adipose tissue [ 8 ]. IL-6 participates in the development of inflammation in the course of many cancers: breast, prostate, colon, lung, stomach and brain [ 11 ]. The overproduction of IL-6 contributes to the promotion of processes conducive to the breakdown of muscle tissue (attempts have been made to use this parameter to monitor the nutritional status of the patient), but it is worth noting that in some cases, cachexia may develop without a marked increase in typical pro-inflammatory cytokines (including IL-6) [ 12 , 13 ].…”