Effects Of Myokines Research Articles

Effects of Exercise-Induced Changes in Myokine Expression on the Tumor Microenvironment.

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.

Abstract B092: Myokine signaling blockade prevents androgen deprivation therapy-induced sarcopenia and promotes prostate tumor regression

Abstract One of the most significant side effects of androgen-deprivation therapy (ADT), the first-line therapy for recurrent and metastatic prostate cancer (PrCa), is sarcopenia (loss of skeletal muscle mass and function). ADT produces a significant disability syndrome in PrCa patients known as obese frailty. Use of ADT has been increasing such that side effects increasingly impact patient quality of life, and result in nursing home placement. The sarcopenia and functional loss of strength is recapitulated following castration of “middle-aged,” but not younger, male mice. In this model all five muscle-regulating TGFß superfamily members, known as myokines, are upregulated in distinctive temporal patterns during sarcopenia development. Complete myokine blockade fully restores muscle mass and strength in castrated mice. We castrated 6- to 9-month-old PbCre4 x PTENfl/fl PrCa-bearing mice and measured tumor volume (by high-frequency ultrasound), body composition (by NMR), muscle mass, fat mass, grip strength, and expression of TGFß family members. Tumor-bearing mice were treated with ActRIIB-Fc (or vehicle) to block myokine signaling; additional tumor-bearing mice were sacrificed biweekly to monitor myokine levels. In an autochthonous mouse model of PrCa, castration-induced changes closely resemble the loss of skeletal muscle strength and body composition that occurs in ADT treated patients. The reduction in muscle strength is comparable to that seen in patients. ADT reduces the mass of individual skeletal muscles, overall LBM, and grip strength. We examined the expression of myokines following castration and found that muscle levels of free dimeric myostatin, the activins, and GDF11 all increase over time, but with distinctive kinetics. Functionally, ActIIRB-Fc, which binds and blocks myokines, inhibits sarcopenia in our model, indicating that the myokines mediate ADT-induced sarcopenia. Surprisingly, this myokine inhibition also induced prostate tumor regression in the absence of ADT, suggesting a protumorigenic effect of myokines. Myokine inhibition also increased the rate of castration-induced prostate tumor regression in this model. In the tumor tissue and in the circulation, as in the muscle tissue of these mice, some of the myokines also increase post-castration. Myokines mediate the induction of sarcopenia following castration, and may also mediate tumor growth. These results suggest that myokines might be both biomarkers and potential targets for therapy to reduce this comorbidity in PrCa patients and may also control tumor growth directly. Citation Format: Chunliu Pan, Yanni Zulia, Kent L. Nasituk. Myokine signaling blockade prevents androgen deprivation therapy-induced sarcopenia and promotes prostate tumor regression [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B092.

Effects of myokines on bone.

The links between muscle and bone have been recently examined because of the increasing number of patients with osteoporosis and sarcopenia. Myokines are skeletal muscle-derived humoral cytokines and growth factors, which exert physiological and pathological functions in various distant organs, including the regulation of glucose, energy and bone metabolism. Myostatin is a crucial myokine, the expression of which is mainly limited to muscle tissues. The inhibition of myostatin signaling increases bone remodeling, bone mass and muscle mass, and it may provide a target for the treatment of both sarcopenia and osteoporosis. As myostatin is involved in osteoclast formation and bone destruction in rheumatoid arthritis, myostatin may be a target myokine for the treatment of accelerated bone resorption and joint destruction in rheumatoid arthritis. Numerous other myokines, including transforming growth factor-β, follistatin, insulin-like growth factor-I, fibroblast growth factor-2, osteoglycin, FAM5C, irisin, interleukin (IL)-6, leukemia inhibitory factor, IL-7, IL-15, monocyte chemoattractant protein-1, ciliary neurotrophic factor, osteonectin and matrix metalloproteinase 2, also affect bone cells in various manners. However, the effects of myokines on bone metabolism are largely unknown. Further research is expected to clarify the interaction between muscle and bone, which may lead to greater diagnosis and the development of the treatment for muscle and bone disorders, such as osteoporosis and sarcopenia.