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Sports Medicine International Open 2024In this narrative review, we summarize the direct and indirect effects that myokines have on the tumor microenvironment. We took studies of various cancer types and... (Review)
Review
In this narrative review, we summarize the direct and indirect effects that myokines have on the tumor microenvironment. We took studies of various cancer types and species into account. Systematic reviews and meta-analyses that matched the search terms were also considered. We searched databases for six months. As a narrative approach was chosen, no data was analyzed or reanalyzed. The goal of this narrative review is to create an overview on the topic to identify research gaps and answer the questions as to whether myokine expression may be relevant in cancer research in regard to the tumor microenvironment. Six commonly known myokines were chosen. We found strong links between the influence exercise has on interleukin-6, oncostatin M, secreted protein acidic and rich in cysteine, and irisin in the context of tumor progression and inhibition via interactions with the tumor microenvironment. It became clear that the effects of myokines on the tumor microenvironment can vary and contribute to disease progression or regression. Interactions among myokines and immune cells must also be considered and require further investigation. To date, no study has shown a clear connection, while multiple studies suggest further investigation of the topic, similar to the effects of exercise on myokine expression.
PubMed: 38933599
DOI: 10.1055/a-2283-1663 -
BioRxiv : the Preprint Server For... Jun 2024Vagal sensory neurons convey sensations from internal organs along the vagus nerve to the brainstem. Pruriceptors are a subtype of neurons that transmit itch and induce...
Vagal sensory neurons convey sensations from internal organs along the vagus nerve to the brainstem. Pruriceptors are a subtype of neurons that transmit itch and induce pruritus. Despite extensive research on the molecular mechanisms of itch, studies focusing on pruriceptors in the vagal ganglia still need to be explored. In this study, we characterized vagal pruriceptor neurons by their responsiveness to pruritogens such as lysophosphatidic acid, -alanine, chloroquine, and the cytokine oncostatin M. We discovered that lung-resident basophils produce oncostatin M and that its release can be induced by engagement of FcRI. Oncostatin M then sensitizes multiple populations of vagal sensory neurons, including Tac1 and MrgprA3 neurons in the jugular ganglia. Finally, we observed an increase in oncostatin M release in mice sensitized to the house dust mite or to the fungal allergen , highlighting a novel mechanism through which basophils and vagal sensory neurons may communicate during type I hypersensitivity diseases such as allergic asthma.
PubMed: 38915548
DOI: 10.1101/2024.06.11.598517 -
Journal of Cachexia, Sarcopenia and... Jun 2024Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted...
BACKGROUND
Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations.
METHODS
This hypothesis-generating analysis used biospecimens collected from a multi-centre 2 × 2 factorial randomized design of 116 patients with stage I-III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log-transformed, and main effects analyses were conducted using linear mixed-effects regression models. The type I error rate was controlled with the Holm sequential testing procedure.
RESULTS
Randomization to exercise increased leukaemia inhibitory factor (1.26 pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P = 0.001) and interleukin-15 (2.23 pg/mL, 95% CI: 0.87, 3.60; adjusted P = 0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (-2.69 pg/mL, 95% CI: -4.31, -1.07; adjusted P = 0.014) and interleukin-15 (-1.74 pg/mL, 95% CI: -2.79, -0.69; adjusted P = 0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons.
CONCLUSIONS
This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis-generating observation warrants further basic, translational and clinical investigation and replication.
PubMed: 38887915
DOI: 10.1002/jcsm.13509 -
Nutrition Research and Practice Jun 2024Breast cancer is considered a serious health issue worldwide and is influenced by risk factors, including physical inactivity and unhealthy diet. Myokines secreted by...
BACKGROUND/OBJECTIVES
Breast cancer is considered a serious health issue worldwide and is influenced by risk factors, including physical inactivity and unhealthy diet. Myokines secreted by muscles during physical activity play a crucial role in cancer development and the immune system. Genistein (Gen), an isoflavone primarily in legumes, induces anti-cancer activity by regulating cancer stem cells (CSCs). Therefore, this study investigated the potential anti-cancer effect of a combination of myokine and Gen on the human breast cancer MCF-7 cells.
MATERIALS/METHODS
MCF-7, a human breast cancer cell line, was used for study. The cell viability of MCF-7 cells was evaluated in response to treatment with myokines, irisin (Iri), oncostatin M (OSM), and Gen using the MTT assay. Clonogenic and sphere formation assays were used to evaluate the self-renewal capacity of breast CSCs. The mRNA expression levels of stem cell markers were analyzed in MCF-7 breast cancer cells.
RESULTS
Administering Iri or OSM with Gen significantly inhibited the self-renewal capacity of MCF-7 cells. In addition, mRNA expression of breast CSC markers and , which are characteristic of CSCs, was suppressed by both myokine and Gen. However, combining Iri or OSM with Gen was the most effective treatment.
CONCLUSION
These results suggested that combining Iri or OSM with Gen has an additive effect on breast CSCs by regulating self-renewal capacity and expression of CSCs markers. Therefore, the combination of myokines and Gen may have the therapeutic potential for treating breast cancer and improving the quality of life of cancer patients.
PubMed: 38854472
DOI: 10.4162/nrp.2024.18.3.436 -
Biomedicine & Pharmacotherapy =... Jul 2024Mitoxantrone resistant variant of SW620 line was developed, characterized and subsequently used as a model system to determine oncostatin M ability to modulate MDR...
Mitoxantrone resistant variant of SW620 line was developed, characterized and subsequently used as a model system to determine oncostatin M ability to modulate MDR phenomenon. The selection regimen allowed for overexpression of ABCG2 and ABCB1 both at the RNA and protein level, which was further confirmed by functional assays. Oncostatin M supplementation resulted in partial reversal of MDR phenotype by decreasing overexpression of ABCG2 demonstrating for the first time the ability of this cytokine for selective down-regulation of one of MDR proteins.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; Mitoxantrone; Drug Resistance, Neoplasm; Humans; Neoplasm Proteins; Oncostatin M; Cell Line, Tumor; Drug Resistance, Multiple; ATP Binding Cassette Transporter, Subfamily B
PubMed: 38850649
DOI: 10.1016/j.biopha.2024.116861 -
NPJ Precision Oncology Jun 2024Chemotherapy such as cisplatin is widely used to treat ovarian cancer either before or after surgical debulking. However, cancer relapse due to chemotherapy resistance...
Chemotherapy such as cisplatin is widely used to treat ovarian cancer either before or after surgical debulking. However, cancer relapse due to chemotherapy resistance is a major challenge in the treatment of ovarian cancer. The underlying mechanisms related to chemotherapy resistance remain largely unclear. Therefore, identification of effective therapeutic strategies is urgently needed to overcome therapy resistance. Transcriptome-based analysis, in vitro studies and functional assays identified that cisplatin-resistant ovarian cancer cells express high levels of OSMR compared to cisplatin sensitive cells. Furthermore, OSMR expression associated with a module of integrin family genes and predominantly linked with integrin αV (ITGAV) and integrin β3 (ITGB3) for cisplatin resistance. Using ectopic expression and knockdown approaches, we proved that OSMR directly regulates ITGAV and ITGB3 gene expression through STAT3 activation. Notably, targeting OSMR using anti-OSMR human antibody inhibited the growth and metastasis of ovarian cancer cells and sensitized cisplatin treatment. Taken together, our results underscore the pivotal role of OSMR as a requirement for cisplatin resistance in ovarian cancer. Notably, OSMR fostered the expression of a distinct set of integrin genes, which in turn resulted into a crosstalk between OSMR and integrins for signaling activation that is critical for cisplatin resistance. Therefore, targeting OSMR emerges as a promising and viable strategy to reverse cisplatin-resistance in ovarian cancer.
PubMed: 38839865
DOI: 10.1038/s41698-024-00593-y -
Cardiology and Cardiovascular Medicine 2024Atherosclerosis is a chronic inflammatory disease that leads to acute embolism via the formation of atherosclerotic plaques. Plaque formation is first induced by fatty...
Atherosclerosis is a chronic inflammatory disease that leads to acute embolism via the formation of atherosclerotic plaques. Plaque formation is first induced by fatty deposition along the arterial intima. Inflammation, bacterial infection, and the released endotoxins can lead to dysfunction and phenotypic changes of vascular smooth muscle cells (VSMCs), advancing the plaque from stable to unstable form and prone to rupture. Stable plaques are characterized by increased VSMCs and less inflammation while vulnerable plaques develop due to chronic inflammation and less VSMCs. Oncostatin M (OSM), an inflammatory cytokine, plays a role in endothelial cells and VSMC proliferation. This effect of OSM could be modulated by p27, a cyclin-dependent kinase (CDK) inhibitor. However, the role of OSM in plaque vulnerability has not been investigated. To better understand the role of OSM and its downstream signaling including p27 in plaque vulnerability, we characterized the previously collected carotid arteries from hyperlipidemic Yucatan microswine using hematoxylin and eosin stain, Movat Pentachrome stain, and gene and protein expression of OSM and p27 using immunostaining and real-time polymerase chain reaction. OSM and p27 expression in carotid arteries with angioplasty and treatment with either scrambled peptide or LR12, an inhibitor of triggering receptor expressed on myeloid cell (TREM)-1, were compared between the experimental groups and with contralateral carotid artery. The results of this study elucidated the presence of OSM and p27 in carotid arteries with plaque and their association with arterial plaque and vulnerability. The findings suggest that targeting OSM and p27 axis regulating VSMC proliferation may have therapeutic significance to stabilize plaque.
PubMed: 38817407
DOI: 10.26502/fccm.92920380 -
Neural Regeneration Research Dec 2024
PubMed: 38808986
DOI: 10.4103/NRR.NRR-D-23-02011 -
Journal of Biomedical Research May 2024Macrophages mediated inflammatory response is crucial for the recovery of skeletal muscle following ischemia. Thus, it's necessary to exploit macrophages based...
Macrophages mediated inflammatory response is crucial for the recovery of skeletal muscle following ischemia. Thus, it's necessary to exploit macrophages based therapeutic targets for ischemic disease. Here, we found mRNA level of SR-A1 was elevated in patients with critical limb ischemia by analysis of gene expression omnibus (GEO) database. Then we investigated the role and the underlined mechanisms of macrophage SR-A1 in a mouse HLI model. Compared with the SR-A1 mice, the Lyz /SR-A1 (SR-A1 ) mice showed significantly lower laser doppler blood flow in the ischemic limb at day 7 after HLI. Consistently, histological analysis exhibited that ischemic limb of SR-A1 mice displayed more sever and sustained necrotic morphology, inflammation and fibrosis, decreased vessel density and regeneration rate, compared with which of control SR-A1 mice. Furthermore, restoration of wild-type myeloid cells to SR-A1 knock-out mice effectively relieved the doppler perfusion in the ischemic limb and restrained skeletal muscle damage 7 days post HLI. In line with findings, when co-cultivating macrophages with the mouse myoblast line C2C12, SR-A1 bone marrow macrophage significantly inhibited myoblast differentiation . Mechanically, SR-A1 enhanced skeletal muscle regeneration response to HLI by inhibiting the oncostatin M (OSM) production via suppressed NF-κB signaling activation. These results indicates that SR-A1 is a promising candidate molecule to improve tissue repair and regeneration in peripheral ischemic arterial disease.
PubMed: 38807379
DOI: 10.7555/JBR.38.20240117 -
Acta Cardiologica Sinica May 2024The use of high-sensitivity troponin levels increases the sensitivity of the diagnosis of non-ST elevation myocardial infarction (NSTEMI). However, the inclusion of...
BACKGROUND
The use of high-sensitivity troponin levels increases the sensitivity of the diagnosis of non-ST elevation myocardial infarction (NSTEMI). However, the inclusion of other factors in the differential diagnosis, apart from atherothrombosis causing myocardial injury, decreases the specificity of high-sensitivity troponin. In this study, we compared the efficacy of high-sensitivity troponin with serum oncostatin M in NSTEMI cases with elevated urea and creatinine.
METHODS
This study was performed with a prospective cross-sectional sample. Ninety participants with coronary angiography performed due to a preliminary diagnosis of NSTEMI were included. High-sensitivity troponin I, creatine kinase-MB, lactate dehydrogenase, serum transaminase and oncostatin M levels were quantitatively measured for the first 4-8 hours from the onset of symptoms. All participants had coronary angiography performed within the first 12 hours after attending the emergency service. Based on coronary angiography data, patients with significant coronary stenosis or occlusion detected during coronary angiography were defined as group A, and patients with no occlusion in the coronary artery and who did not require an additional interventional procedure were defined as group B. The SYNTAX 2 score was used to determine the severity of coronary artery disease.
RESULTS
Patients in both groups A and B had similar age, sex distribution and comorbidities. Group A had higher serum urea, creatinine, oncostatin M and high-sensitivity troponin I values than group B. With 585 pg/ml as the cut-off value, serum oncostatin M had a sensitivity of 88.6% and specificity of 85% for the diagnosis of NSTEMI. Logistic regression multivariate analysis showed that serum oncostatin M and high-sensitivity troponin I values had diagnostic efficacy for NSTEMI. Serum oncostatin M was found to be more effective than high-sensitivity troponin I in patients with elevated urea and creatinine.
CONCLUSIONS
Serum oncostatin M had similar sensitivity and specificity for NSTEMI diagnosis as high-sensitivity troponin I. Serum OSM can especially be considered as a complementary diagnostic biomarker for NSTEMI in patients with renal dysfunction.
PubMed: 38779167
DOI: 10.6515/ACS.202405_40(3).20240128A