Beneficial role of regular physical exercise on tumor development and different susceptibility of muscle fibers to cancer-induced wasting in mice

Abstract

The present thesis is supported by a literature review that overviewed the current theoretical knowledge about the implications of the vascularization on the tumor microenvironment, and by a systematic review with meta-analysis that allowed us to systematize and quantify the existing evidence about the effects of vascularization on tumor growth, in animal models. The experimental work was based on a systematic review with meta-analysis of animal studies, regarding the effects of physical exercise on tumor vascularization, and on two different protocols, one performed with C57BL/6 male mice, from which resulted two studies to investigate the effects of regular voluntary running on tumor growth, on its vascularization and lymphocytic infiltration, while the other involved CR (CD1) male mice, to describe the impact of cancer development on different types of skeletal muscle. The first systematic review with meta-analysis showed that the reduction of tumor vascularization induced by anti-angiogenic therapy contributed to the inhibition of its growth. The results from the empirical studies demonstrated that physical exercise improved the tumor vascularization and regular voluntary running attenuated tumor growth, through a decreased proliferation, an increased apoptosis and improved vascularization, a higher quantity of CD8+ T cells and more NKG2D receptors in tumor. We also found that the muscle wasting induced by cancer development occurred predominantly in glycolytic muscle, which are mostly composed by type II fibers, sparing the oxidative muscles, constituted manly of type I fibers and with an increased contractile activity. These results allow us to conclude that in mice, regular wheel running attenuates tumor growth, improves tumor vascularization and the immune cells' access to the tumor, and the glycolytic muscles are more affected by cancer development.