The cachectic mediator proteolysis inducing factor activates NF-κB and STAT3 in human Kupffer cells and monocytes

Watchorn, Tammy; Dowidar, Nabil; Dejong, Cornelis H. C.; Waddell, Ian D.; Garden, O. James; Ross, James D.

doi:10.3892/ijo.27.4.1105

Cited by 22 publications

(24 citation statements)

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“…The effect occurs through the NFB and STAT3 transcriptional pathways. A similar effect was observed in human Kupffer cells and monocytes resulting in the production of TNF-␣, IL-6, and IL-8 (273). PIF also induced syndecan shedding from human vein endothelial cells, which has been suggested to be related to metastasis, as well as patient mortality.…”

Section: Apoptosis In Skeletal Musclesupporting

confidence: 49%

Mechanisms of Cancer Cachexia

Tisdale

2009

Physiological Reviews

977

1,061

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Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body mass. An increased resting energy expenditure is seen, possibly arising from an increased thermogenesis in skeletal muscle due to an increased expression of uncoupling protein, and increased operation of the Cori cycle. Loss of adipose tissue is due to an increased lipolysis by tumor or host products. Loss of skeletal muscle in cachexia results from a depression in protein synthesis combined with an increase in protein degradation. The increase in protein degradation may include both increased activity of the ubiquitin-proteasome pathway and lysosomes. The decrease in protein synthesis is due to a reduced level of the initiation factor 4F, decreased elongation, and decreased binding of methionyl-tRNA to the 40S ribosomal subunit through increased phosphorylation of eIF2 on the α-subunit by activation of the dsRNA-dependent protein kinase, which also increases expression of the ubiquitin-proteasome pathway through activation of NFκB. Tumor factors such as proteolysis-inducing factor and host factors such as tumor necrosis factor-α, angiotensin II, and glucocorticoids can all induce muscle atrophy. Knowledge of the mechanisms of tissue destruction in cachexia should improve methods of treatment.

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Section: Apoptosis In Skeletal Musclesupporting

confidence: 49%

Mechanisms of Cancer Cachexia

Tisdale

2009

Physiological Reviews

977

1,061

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“…One molecule of relevance seems to be proteolysis-inducing factor (PIF), resulting in increased production of proinflammatory cytokines, including IL-8 and IL-6, notably via stimulation of the transcription factor nuclear factor kappa B (35,36). There has been a reported association between PIF expression and weight loss in advanced cancer patients (37); however, this has not been confirmed in a recent relevant study in lung cancer patients (38).…”

Section: Discussionmentioning

confidence: 92%

Baseline Plasma Levels of Interleukin-8 in Stage IV Non-Small-Cell Lung Cancer Patients: Relationship With Nutritional Status and Prognosis

Gioulbasanis

Patrikidou

Kitikidou

et al. 2012

Nutrition and Cancer

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Interleukin (IL)-8 promotes cellular proliferation and angiogenesis in patients with non-small-cell lung cancer (NSCLC) and may be related to cachexia. Our aim was to investigate the relationship of IL-8 levels with nutritional status, and clinical outcome of patients with NSCLC. Patients with metastatic NSCLC referred for first-line therapy were eligible. Baseline IL-8 levels were measured in plasma. The Mini Nutritional Assessment (MNA) was used for the evaluation of the nutritional status, and patients were classified into 3 groups: A (score 24-30) "well nourished," B (score 17-23.5) "risk of malnutrition," and C (0-16.5) "malnourishment." Response to first-line chemotherapy, time-to-tumor progression (TTP), and overall survival (OS) were also recorded. In total, 114 patients (101 males, 88.5%; mean age = 67.5 yr) were evaluated. Performance status was 0-1 in 62% of the patients. According to the MNA, the majority of patients (71%) was either at nutritional risk or malnourished. IL-8 levels were significantly different between MNA groups (P = 0.023) and correlated with TTP (P = 0.013) and OS (P = 0.001) in univariate analysis. Baseline IL-8 levels correlate with the nutritional status of patients with metastatic NSCLC, suggesting that this cytokine may be related with cachexia.

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“…Alternatively, the Jak2/ Stat3 system could be active as it is reported to stimulate cancer cachexia (12)(13)(14). The Stat3 signaling pathway could be involved because IL-6 and other members of the IL-6 family (e.g.…”

mentioning

confidence: 99%

Inhibition of Stat3 Activation Suppresses Caspase-3 and the Ubiquitin-Proteasome System, Leading to Preservation of Muscle Mass in Cancer Cachexia

Silva

Dong

et al. 2015

Journal of Biological Chemistry

178

218

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Background:No reliable treatment exists for cancer-related muscle loss. Results: In muscles of mice with cancer, p-Stat3 stimulates proteolysis by activating caspase-3 and the ubiquitin-proteasome system through a C/EBP␦ and myostatin pathway. Conclusion: Inhibition of Stat3 suppresses cancer-induced muscle losses.Significance: A small-molecule Stat3 inhibitor could be integrated into therapeutic strategies for preventing cancer-induced muscle losses.

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The cachectic mediator proteolysis inducing factor activates NF-κB and STAT3 in human Kupffer cells and monocytes

Cited by 22 publications

References 0 publications

Mechanisms of Cancer Cachexia

Mechanisms of Cancer Cachexia

Baseline Plasma Levels of Interleukin-8 in Stage IV Non-Small-Cell Lung Cancer Patients: Relationship With Nutritional Status and Prognosis

Inhibition of Stat3 Activation Suppresses Caspase-3 and the Ubiquitin-Proteasome System, Leading to Preservation of Muscle Mass in Cancer Cachexia

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