Progressive development of melanoma-induced cachexia differentially impacts organ systems in mice

Graça, Flávia A.; Stephan, Anna; Wang, Yongdong; Shirinifard, Abbas; Jiao, Jianqin; Vogel, Peter; Labelle, Myriam; Demontis, Fabio

doi:10.1016/j.celrep.2022.111934

Cited by 5 publications

(6 citation statements)

References 122 publications

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“…Frozen TA muscle sections (10 μm-thick) were mounted on positively charged glass slides (Superfrost Plus; Thermo Fisher Scientific, Waltham, MA), and dried at room temperature for 1 h. Tissue sections were then stained with H&E according to standard procedures 142 .…”

Section: Methodsmentioning

confidence: 99%

Platelet-derived chemokines promote skeletal muscle regeneration by guiding neutrophil recruitment to injured muscles

et al. 2023

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Skeletal muscle regeneration involves coordinated interactions between different cell types. Injection of platelet-rich plasma is circumstantially considered an aid to muscle repair but whether platelets promote regeneration beyond their role in hemostasis remains unexplored. Here, we find that signaling via platelet-released chemokines is an early event necessary for muscle repair in mice. Platelet depletion reduces the levels of the platelet-secreted neutrophil chemoattractants CXCL5 and CXCL7/PPBP. Consequently, early-phase neutrophil infiltration to injured muscles is impaired whereas later inflammation is exacerbated. Consistent with this model, neutrophil infiltration to injured muscles is compromised in male mice with Cxcl7-knockout platelets. Moreover, neo-angiogenesis and the re-establishment of myofiber size and muscle strength occurs optimally in control mice post-injury but not in Cxcl7ko mice and in neutrophil-depleted mice. Altogether, these findings indicate that platelet-secreted CXCL7 promotes regeneration by recruiting neutrophils to injured muscles, and that this signaling axis could be utilized therapeutically to boost muscle regeneration.

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Section: Methodsmentioning

confidence: 99%

Platelet-derived chemokines promote skeletal muscle regeneration by guiding neutrophil recruitment to injured muscles

et al. 2023

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“…In parallel, control mice were housed in cages without engaging in exercise. Starting from the second week of the study, 1 × 10 5 B16F10 cells were intravenously injected into the mice through the tail vein to induce cancer cachexia [ 9 , 22 ]. ( Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, cachexia exhibits varied impacts on different tissues, with the heart and skeletal muscle particularly affected in the early stages [ 9 ]. Patients with cancer cachexia often manifest impaired cardiac function [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Low-intensity exercise training improves systolic function of heart during metastatic melanoma-induced cachexia in mice

Wang,

Chen

et al. 2024

Heliyon

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“…Although the mechanisms underlying the induction of cachexia are not yet known, some central nervus system (CNS)-mediated cancer symptoms, such as anorexia and fatigue, support the idea that one of these mechanisms could be brain dysregulation during malignancy. Since cachexia has been shown to affect the expression of key metabolism-related factors in the brain, resulting in a reduction of the intracellular uptake of glucose, and promote an Alzheimer's disease-like neuroinflammatory pathway via circulating endotoxins, brain inflammation has been proposed to be one of its key drivers [ 10 , 11 ]. Among brain regions, the hypothalamus mainly corresponds to cachexia, given its anatomic location and its ability to access peripheral signals directly due to attenuation of the blood–brain barrier.…”

Section: Introductionmentioning

confidence: 99%

Peripheral-central network analysis of cancer cachexia status accompanied by the polarization of hypothalamic microglia with low expression of inhibitory immune checkpoint receptors

Suda,

Nakamura,

Matsuyama

et al. 2024

Mol Brain

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While the excessive inflammation in cancer cachexia is well-known to be induced by the overproduction of inflammatory mediators in the periphery, microflora disruption and brain dysfunction are also considered to contribute to the induction of cancer cachexia. Hypothalamic microglia play a crucial role in brain inflammation and central-peripheral immune circuits via the production of inflammatory mediators. In the present study, we evaluated possible changes in excessive secretion of gut microbiota-derived endotoxin and the expression timeline of several inflammation-regulatory mediators and their inhibiting modulators in hypothalamic microglia of a mouse model of cancer cachexia following transplantation of pancreatic cancer cells. We demonstrated that the plasma level of lipopolysaccharide (LPS) was significantly increased with an increase in anaerobic bacteria, especially Firmicutes, in the gut at the late stage of tumor-bearing mice that exhibited dramatic appetite loss, sarcopenia and severe peripheral immune suppression. At the early stage, in which tumor-bearing mice had not yet displayed “cachexia symptoms”, the mRNA expression of pro-inflammatory cytokines, but not of the neurodegenerative and severe inflammatory modulator lipocalin-2 (LCN2), was significantly increased, whereas at the late “cachexia stage”, the level of LCN2 mRNA was significantly increased along with significant decreases in levels of inhibitory immune checkpoint receptors programmed death receptor-1 (PD-1) and CD112R in hypothalamic microglia. In addition, a high density of activated neurons in the paraventricular nucleus (PVN) of the hypothalamus region and a significant increase in corticosterone secretion were found in cachexia model mice. Related to the cachexia state, released corticosterone was clearly increased in normal mice with specific activation of PVN neurons. A marked decrease in the natural killer cell population was also observed in the spleen of mice with robust activation of PVN neurons as well as mice with cancer cachexia. On the other hand, in vivo administration of LPS in normal mice induced hypothalamic microglia with low expression of inhibitory immune checkpoint receptors. These findings suggest that the induction of cancer cachexia may parallel exacerbation of the hypothalamic inflammatory status with polarization to microglia expressed with low levels of inhibitory immune checkpoint receptors following LPS release from the gut microflora.

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Progressive development of melanoma-induced cachexia differentially impacts organ systems in mice

Cited by 5 publications

References 122 publications

Platelet-derived chemokines promote skeletal muscle regeneration by guiding neutrophil recruitment to injured muscles

Platelet-derived chemokines promote skeletal muscle regeneration by guiding neutrophil recruitment to injured muscles

Low-intensity exercise training improves systolic function of heart during metastatic melanoma-induced cachexia in mice

Peripheral-central network analysis of cancer cachexia status accompanied by the polarization of hypothalamic microglia with low expression of inhibitory immune checkpoint receptors

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