Tumor-derived cytokines impair myogenesis and alter the skeletal muscle immune microenvironment

Hogan, Kelly A.; Cho, Dong Seong; Arneson, Paige C.; Samani, Adrienne; Palines, Patrick A.; Yang, Yanan; Doles, Jason D.

doi:10.1016/j.cyto.2017.11.006

Cited by 40 publications

(35 citation statements)

References 52 publications

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“…Animal models, including the C26 colon adenocarcinoma mouse model, have also revealed associations between cancer and cardiac atrophy and remodeling (131,132). Although the cancer-derived mediators of cardiac atrophy have not yet been identified, studies suggest that tumor-derived mediators, such as proinflammatory cytokines, promote muscle wasting (133,134). These experimental data and clinical associations strongly suggest deeper connections in the organ crosstalk between cancer and the heart.…”

Section: Cardioncologymentioning

confidence: 99%

Organ System Crosstalk in Cardiometabolic Disease in the Age of Multimorbidity

Oishi

Manabe

2020

Front. Cardiovasc. Med.

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The close association among cardiovascular, metabolic, and kidney diseases suggests a common pathological basis and significant interaction among these diseases. Metabolic syndrome and cardiorenal syndrome are two examples that exemplify the interlinked development of disease or dysfunction in two or more organs. Recent studies have been sorting out the mechanisms responsible for the crosstalk among the organs comprising the cardiovascular, metabolic, and renal systems, including heart-kidney and adipose-liver signaling, among many others. However, it is also becoming clear that this crosstalk is not limited to just pairs of organs, and in addition to organ-organ crosstalk, there are also organ-system and organ-body interactions. For instance, heart failure broadly impacts various organs and systems, including the kidney, liver, lung, and nervous system. Conversely, systemic dysregulation of metabolism, immunity, and nervous system activity greatly affects heart failure development and prognosis. This is particularly noteworthy, as more and more patients present with two or more coexisting chronic diseases or conditions (multimorbidity) due in part to the aging of society. Advances in treatment also contribute to the increase in multimorbidity, as exemplified by cardiovascular disease in cancer survivors. To understand the mechanisms underlying the increasing burden of multimorbidity, it is vital to elucidate the multilevel crosstalk and communication within the body at the levels of organ systems, tissues, and cells. In this article, we focus on chronic inflammation as a key common pathological basis of cardiovascular and metabolic diseases, and discuss emerging mechanisms that drive chronic inflammation in the context of multimorbidity.

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Section: Cardioncologymentioning

confidence: 99%

Organ System Crosstalk in Cardiometabolic Disease in the Age of Multimorbidity

Oishi

Manabe

2020

Front. Cardiovasc. Med.

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“…Loss in both body weight and lean mass is a hallmark of CAW. Many studies have implicated heightened inflammatory signaling as a driver of CAW [22][23][24]. We quantitatively assessed concentrations of 31 cytokines in the serum of tumor-bearing and vehicle animals (EveTechnologies) (n = 5 vehicle and 4 tumor).…”

Section: Lung Cancer-associated Molecular Changes In Serum and Skeletmentioning

confidence: 99%

A novel transplantable model of lung cancer-associated tissue loss and disrupted muscle regeneration

2020

Self Cite

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Background: Cancer-associated muscle wasting (CAW), a symptom of cancer cachexia, is associated with approximately 20% of lung cancer deaths and remains poorly characterized on a mechanistic level. Current animal models for lung cancer-associated cachexia are limited in that they (1) primarily employ flank transplantation methods, (2) have short survival times not reflective of the patient condition, and (3) are typically performed in young mice not representative of mean patient age. This study investigates a new model for lung cancerassociated cachexia that can address these issues and also implicates muscle regeneration as a contributor to CAW. Methods: We used tail vein injection as a method to introduce tumor cells that seed primarily in the lungs of mice. Body composition of tumor-bearing mice was longitudinally tracked using NMR-based, echo magnetic resonance imaging (echoMRI). These data were combined with histological and molecular assessments of skeletal muscle to provide a complete analysis of muscle wasting.Results: In this new lung CAW model, we observed (1) progressive loss in whole body weight, (2) progressive loss of lean and fat mass, (3) a circulating cytokine/inflammatory profile similar to that seen in other models of CAW, (4) histological changes associated with muscle wasting, and (5) molecular changes in muscle that implicate suppression of muscle repair/regeneration. Finally, we show that survival can be extended without lessening CAW by titrating injected cell number.Conclusions: Overall, this study describes a new model of CAW that could be useful for further studies of lung cancer-associated wasting and accompanying changes in the regenerative capacity of muscle. Additionally, this model addresses many recent concerns with existing models such as immunocompetence, tumor location, and survival time.

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“…It has been well established that cytokines secreted by host immune cells in response to tumors and/or by the tumor itself are associated with muscle wasting and functional limitations [30,31]. High plasma levels of IL-6, TNF-α, INF-γ, and IL-1β have been observed in both tumor-bearing animals and cachectic cancer patients [32,33]. Fatigued women who survive breast cancer have significantly higher serum levels of IL-1ra, sTNF-RII, and neopterin than non-fatigued women [34].…”

Section: Altered Cytokines Contribute To Functional Limitations In Brmentioning

confidence: 99%

Systemic Actions of Breast Cancer Facilitate Functional Limitations

Wang

Nakshatri

2020

Cancers

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Breast cancer is a disease of a specific organ, but its effects are felt throughout the body. The systemic effects of breast cancer can lead to functional limitations in patients who suffer from muscle weakness, fatigue, pain, fibromyalgia, or many other dysfunctions, which hasten cancer-associated death. Mechanistic studies have identified quite a few molecular defects in skeletal muscles that are associated with functional limitations in breast cancer. These include circulating cytokines such as TNF-α, IL-1, IL-6, and TGF-β altering the levels or function of myogenic molecules including PAX7, MyoD, and microRNAs through transcriptional regulators such as NF-κB, STAT3, and SMADs. Molecular defects in breast cancer may also include reduced muscle mitochondrial content and increased extracellular matrix deposition leading to energy imbalance and skeletal muscle fibrosis. This review highlights recent evidence that breast cancer-associated molecular defects mechanistically contribute to functional limitations and further provides insights into therapeutic interventions in managing functional limitations, which in turn may help to improve quality of life in breast cancer patients.

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Tumor-derived cytokines impair myogenesis and alter the skeletal muscle immune microenvironment

Cited by 40 publications

References 52 publications

Organ System Crosstalk in Cardiometabolic Disease in the Age of Multimorbidity

Organ System Crosstalk in Cardiometabolic Disease in the Age of Multimorbidity

A novel transplantable model of lung cancer-associated tissue loss and disrupted muscle regeneration

Systemic Actions of Breast Cancer Facilitate Functional Limitations

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