scholarly journals Inflammation Based Regulation of Cancer Cachexia

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jill K. Onesti ◽  
Denis C. Guttridge
Keyword(s):  
Quality Of Life ◽  
Skeletal Muscle ◽  
Cancer Cachexia ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Nutritional Intake ◽  
Clinical Implications ◽  
Life Outcomes ◽  
Skeletal Muscle Wasting

Cancer cachexia, consisting of significant skeletal muscle wasting independent of nutritional intake, is a major concern for patients with solid tumors that affects surgical, therapeutic, and quality of life outcomes. This review summarizes the clinical implications, background of inflammatory cytokines, and the origin and sources of procachectic factors including TNF-α, IL-6, IL-1, INF-γ, and PIF. Molecular mechanisms and pathways are described to elucidate the link between the immune response caused by the presence of the tumor and the final result of skeletal muscle wasting.

scholarly journals Exercise as an anti-inflammatory therapy for cancer cachexia: a focus on interleukin-6 regulation

2020 ◽  
Vol 318 (2) ◽  
pp. R296-R310 ◽  
Author(s):  
Hélène N. Daou
Keyword(s):  
Skeletal Muscle ◽  
Systemic Inflammation ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Skeletal Muscle Atrophy ◽  
Ampk Signaling ◽  
Skeletal Muscle Wasting ◽  
Skeletal Muscle Loss ◽  
Anti Inflammatory ◽  
Tumor Growth And Metastasis

Cancer cachexia is a complicated disorder of extreme, progressive skeletal muscle wasting. It is directed by metabolic alterations and systemic inflammation dysregulation. Numerous studies have demonstrated that increased systemic inflammation promotes this type of cachexia and have suggested that cytokines are implicated in the skeletal muscle loss. Exercise is firmly established as an anti-inflammatory therapy that can attenuate or even reverse the process of muscle wasting in cancer cachexia. The interleukin IL-6 is generally considered to be a key player in the development of the microenvironment of malignancy; it promotes tumor growth and metastasis by acting as a bridge between chronic inflammation and cancerous tissue and it also induces skeletal muscle atrophy and protein breakdown. Paradoxically, a beneficial role for IL-6 has also been identified recently, and that is its status as a “founding member” of the myokine class of proteins. Skeletal muscle is an important source of circulating IL-6 in people who participate in exercise training. IL-6 acts as an anti-inflammatory myokine by inhibiting TNFα and improving glucose uptake through the stimulation of AMPK signaling. This review discusses the action of IL-6 in skeletal muscle tissue dysfunction and the role of IL-6 as an “exercise factor” that modulates the immune system. This review also sheds light on the main considerations related to the treatment of muscle wasting in cancer cachexia.

scholarly journals The Adipokines in Cancer Cachexia

2020 ◽  
Vol 21 (14) ◽  
pp. 4860 ◽  
Author(s):  
Michele Mannelli ◽  
Tania Gamberi ◽  
Francesca Magherini ◽  
Tania Fiaschi
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Therapeutic Strategies ◽  
Skeletal Muscle Wasting ◽  
Circulating Levels

Cachexia is a devastating pathology induced by several kinds of diseases, including cancer. The hallmark of cancer cachexia is an extended weight loss mainly due to skeletal muscle wasting and fat storage depletion from adipose tissue. The latter exerts key functions for the health of the whole organism, also through the secretion of several adipokines. These hormones induce a plethora of effects in target tissues, ranging from metabolic to differentiating ones. Conversely, the decrease of the circulating level of several adipokines positively correlates with insulin resistance, metabolic syndrome, diabetes, and cardiovascular disease. A lot of findings suggest that cancer cachexia is associated with changed secretion of adipokines by adipose tissue. In agreement, cachectic patients show often altered circulating levels of adipokines. This review reported the findings of adipokines (leptin, adiponectin, resistin, apelin, and visfatin) in cancer cachexia, highlighting that to study in-depth the involvement of these hormones in this pathology could lead to the development of new therapeutic strategies.

Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness

2008 ◽  
Vol 9 (4) ◽  
pp. 213-228 ◽  
Author(s):  
James G. Ryall ◽  
Jonathan D. Schertzer ◽  
Gordon S. Lynch
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Skeletal Muscle Wasting ◽  
Age Related

scholarly journals JNK signaling contributes to skeletal muscle wasting and protein turnover in pancreatic cancer cachexia

2020 ◽  
Vol 491 ◽  
pp. 70-77 ◽  
Author(s):  
Scott E. Mulder ◽  
Aneesha Dasgupta ◽  
Ryan J. King ◽  
Jaime Abrego ◽  
Kuldeep S. Attri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Protein Turnover ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Jnk Signaling ◽  
Skeletal Muscle Wasting

scholarly journals MicroRNAs in Skeletal Muscle and Hints on Their Potential Role in Muscle Wasting During Cancer Cachexia

2020 ◽  
Vol 10 ◽  
Author(s):  
Gioacchino P. Marceca ◽  
Giovanni Nigita ◽  
Federica Calore ◽  
Carlo M. Croce
Keyword(s):  
Skeletal Muscle ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Phenotypic Alteration ◽  
Specific Tumor ◽  
Non Coding Rnas

Cancer-associated cachexia is a heterogeneous, multifactorial syndrome characterized by systemic inflammation, unintentional weight loss, and profound alteration in body composition. The main feature of cancer cachexia is represented by the loss of skeletal muscle tissue, which may or may not be accompanied by significant adipose tissue wasting. Such phenotypic alteration occurs as the result of concomitant increased myofibril breakdown and reduced muscle protein synthesis, actively contributing to fatigue, worsening of quality of life, and refractoriness to chemotherapy. According to the classical view, this condition is primarily triggered by interactions between specific tumor-induced pro-inflammatory cytokines and their cognate receptors expressed on the myocyte membrane. This causes a shift in gene expression of muscle cells, eventually leading to a pronounced catabolic condition and cell death. More recent studies, however, have shown the involvement of regulatory non-coding RNAs in the outbreak of cancer cachexia. In particular, the role exerted by microRNAs is being widely addressed, and several mechanistic studies are in progress. In this review, we discuss the most recent findings concerning the role of microRNAs in triggering or exacerbating muscle wasting in cancer cachexia, while mentioning about possible roles played by long non-coding RNAs and ADAR-mediated miRNA modifications.

scholarly journals Mitofusin-2 prevents skeletal muscle wasting in cancer cachexia

2016 ◽  
Vol 12 (5) ◽  
pp. 4013-4020 ◽  
Author(s):  
Qiu-Lei Xi ◽  
Bo Zhang ◽  
Yi Jiang ◽  
Hai-Sheng Zhang ◽  
Qing-Yang Meng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Mitofusin 2 ◽  
Skeletal Muscle Wasting

scholarly journals Myostatin is a novel tumoral factor that induces cancer cachexia

2012 ◽  
Vol 446 (1) ◽  
pp. 23-36 ◽  
Author(s):  
Sudarsanareddy Lokireddy ◽  
Isuru Wijerupage Wijesoma ◽  
Sabeera Bonala ◽  
Meng Wei ◽  
Siu Kwan Sze ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Skeletal Muscles ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Transforming Growth Factor ◽  
C2c12 Myotubes ◽  
E3 Ligases ◽  
Molecular Features ◽  
Skeletal Muscle Wasting

Humoral and tumoral factors collectively promote cancer-induced skeletal muscle wasting by increasing protein degradation. Although several humoral proteins, namely TNFα (tumour necrosis factor α) and IL (interleukin)-6, have been shown to induce skeletal muscle wasting, there is a lack of information regarding the tumoral factors that contribute to the atrophy of muscle during cancer cachexia. Therefore, in the present study, we have characterized the secretome of C26 colon cancer cells to identify the tumoral factors involved in cancer-induced skeletal muscle wasting. In the present study, we show that myostatin, a procachectic TGFβ (transforming growth factor β) superfamily member, is abundantly secreted by C26 cells. Consistent with myostatin signalling during cachexia, treating differentiated C2C12 myotubes with C26 CM (conditioned medium) resulted in myotubular atrophy due to the up-regulation of muscle-specific E3 ligases, atrogin-1 and MuRF1 (muscle RING-finger protein 1), and enhanced activity of the ubiquitin–proteasome pathway. Furthermore, the C26 CM also activated ActRIIB (activin receptor type II B)/Smad and NF-κB (nuclear factor κB) signalling, and reduced the activity of the IGF-I (insulin-like growth factor 1)/PI3K (phosphoinositide 3-kinase)/Akt pathway, three salient molecular features of myostatin action in skeletal muscles. Antagonists to myostatin prevented C26 CM-induced wasting in muscle cell cultures, further confirming that tumoral myostatin may be a key contributor in the pathogenesis of cancer cachexia. Finally, we show that treatment with C26 CM induced the autophagy–lysosome pathway and reduced the number of mitochondria in myotubes. These two previously unreported observations were recapitulated in skeletal muscles collected from C26 tumour-bearing mice.

scholarly journals Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lin Zhou ◽  
Tong Zhang ◽  
Wei Shao ◽  
Ruohan Lu ◽  
Lin Wang ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Cancer Cachexia ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Drug Repositioning ◽  
Biochemical Analyses ◽  
Related Proteins ◽  
Metabolic Impairments

Abstract Background Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of the amiloride treatment for ameliorating muscle wasting in murine models of cancer cachexia. Methods The CT26 and LLC tumor cells were subcutaneously injected into mice to induce colon cancer cachexia and lung cancer cachexia, respectively. Amiloride was intraperitoneally injected daily once tumors were formed. Cachexia features of the CT26 model and the LLC model were separately characterized by phenotypic, histopathologic and biochemical analyses. Plasma exosomes and muscle atrophy-related proteins were quantitatively analyzed. Integrative NMR-based metabolomic and transcriptomic analyses were conducted to identify significantly altered metabolic pathways and distinctly changed metabolism-related biological processes in gastrocnemius. Results The CT26 and LLC cachexia models displayed prominent cachexia features including decreases in body weight, skeletal muscle, adipose tissue, and muscle strength. The amiloride treatment in tumor-bearing mice distinctly alleviated muscle atrophy and relieved cachexia-related features without affecting tumor growth. Both the CT26 and LLC cachexia mice showed increased plasma exosome densities which were largely derived from tumors. Significantly, the amiloride treatment inhibited tumor-derived exosome release, which did not obviously affect exosome secretion from non-neoplastic tissues or induce observable systemic toxicities in normal healthy mice. Integrative-omics revealed significant metabolic impairments in cachectic gastrocnemius, including promoted muscular catabolism, inhibited muscular protein synthesis, blocked glycolysis, and impeded ketone body oxidation. The amiloride treatment evidently improved the metabolic impairments in cachectic gastrocnemius. Conclusions Amiloride ameliorates cachectic muscle wasting and alleviates cancer cachexia progression through inhibiting tumor-derived exosome release. Our results are beneficial to understanding the underlying molecular mechanisms, shedding light on the potentials of amiloride in cachexia therapy.

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