Biomarkers of cancer cachexia

Loumaye, Audrey; Thissen, Jean‐Paul

doi:10.1016/j.clinbiochem.2017.07.011

Cited by 89 publications

(108 citation statements)

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“…Such problems may be particularly important in patients admitted to the intensive care unit with sarcopenia being already present. [46][47][48][49] An interesting candidate biomarker Cterminal agrin fragment has been used in patients with HF 50 and in patients after acute stroke. Therefore, androgen deprivation appears to cause selective deficits in the biochemical leg muscle function, which may also play a role in patients with HF in whom the deficiency of anabolic hormones has been reported to play a major role and to have prognostic significance.…”

Section: Screening and Diagnosing Sarcopeniamentioning

confidence: 99%

Muscle wasting and sarcopenia in heart failure: a brief overview of the current literature

Haehling

2018

ESC Heart Failure

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Section: Screening and Diagnosing Sarcopeniamentioning

confidence: 99%

Muscle wasting and sarcopenia in heart failure: a brief overview of the current literature

Haehling

2018

ESC Heart Failure

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“…The most highly studied of these include interleukin‐6 (IL‐6) and tumour necrosis factor‐alpha (TNFα). However, antibodies administered to mice or humans against these molecules have had mixed effectiveness at improving health . More recently, multiplex immunoassays have made possible the measurement of many circulating factors simultaneously in humans and in preclinical mouse models of cancer cachexia, providing a broader picture of the growth and immune‐related factors that may play a role in cachexia .…”

Section: Introductionmentioning

confidence: 99%

“…A difficulty, however, is linking the increases in circulating factors to a causal role in muscle wasting. In addition, different tumour types and different animal species appear to cause wasting by different mechanisms …”

Section: Introductionmentioning

confidence: 99%

“…Pro-inflammatory cytokines and other factors are elevated in mice and humans with cancer cachexia. 6,[12][13][14] The most highly studied of these include interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNFα). However, antibodies administered to mice or humans against these molecules have had mixed effectiveness at improving health.…”

Section: Introductionmentioning

confidence: 99%

“…However, antibodies administered to mice or humans against these molecules have had mixed effectiveness at improving health. 6,12,[14][15][16] More recently, multiplex immunoassays have made possible the measurement of many circulating factors simultaneously in humans and in preclinical mouse models of cancer cachexia, providing a broader picture of the growth and immunerelated factors that may play a role in cachexia. 12,17,18 A difficulty, however, is linking the increases in circulating factors to a causal role in muscle wasting.…”

Section: Introductionmentioning

confidence: 99%

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Tumour‐derived leukaemia inhibitory factor is a major driver of cancer cachexia and morbidity in C26 tumour‐bearing mice

Kandarian

Nosacka

Delitto

et al. 2018

J cachexia sarcopenia muscle

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BackgroundCancer cachexia is a metabolic wasting syndrome that is strongly associated with a poor prognosis. The initiating factors causing fat and muscle loss are largely unknown. Previously, we found that leukaemia inhibitory factor (LIF) secreted by C26 colon carcinoma cells was responsible for atrophy in treated myotubes. In the present study, we tested whether C26 tumour‐derived LIF is required for cancer cachexia in mice by knockout of Lif in C26 cells.MethodsA C26 Lif null tumour cell line was made using CRISPR‐Cas9. Measurements of cachexia were compared in mice inoculated with C26 vs. C26Lif−/− tumour cells, and atrophy was compared in myotubes treated with medium from C26 vs. C26Lif−/− tumour cells. Levels of 25 cytokines/chemokines were compared in serum of mice bearing C26 vs. C26Lif−/− tumours and in the medium from these tumour cell lines.ResultsAt study endpoint, C26 mice showed outward signs of sickness while mice with C26Lif−/− tumours appeared healthy. Mice with C26Lif−/− tumours showed a 55–75% amelioration of body weight loss, muscle loss, fat loss, and splenomegaly compared with mice with C26 tumours (P < 0.05). The heart was not affected by LIF levels because the loss of cardiac mass was the same in C26 and C26Lif−/− tumour‐bearing mice. LIF levels in mouse serum was entirely dependent on secretion from the tumour cells. Serum levels of interleukin‐6 and G‐CSF were increased by 79‐fold and 68‐fold, respectively, in C26 mice but only by five‐fold and two‐fold, respectively, in C26Lif−/− mice, suggesting that interleukin‐6 and G‐CSF increases are dependent on tumour‐derived LIF.ConclusionsThis study shows the first use of CRISPR‐Cas9 knockout of a candidate cachexia factor in tumour cells. The results provide direct evidence for LIF as a major cachexia initiating factor for the C26 tumour in vivo. Tumour‐derived LIF was also a regulator of multiple cytokines in C26 tumour cells and in C26 tumour‐bearing mice. The identification of tumour‐derived factors such as LIF that initiate the cachectic process is immediately applicable to the development of therapeutics to treat cachexia. This is a proof of principle for studies that when carried out in human cells, will make possible an understanding of the factors causing cachexia in a patient‐specific manner.

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