Effect of physical exercise on tumor growth regulating factors of tumor microenvironment: Implications in exercise-dependent tumor growth retardation

Recently, we reported that treadmill exercise renders survival benefits in a murine tumor model of a transplantable lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL), owing to an augmented apoptosis of tumor cells. However, the underlying the mechanisms of the same remained unclear with respect to the role alterations if any in the components of tumor microenvironment following physical exercise. Therefore, in the present we investigated the role of oxygen, pH, lactate and cytokines of tumor micro-environment associated with physical exercise-dependent alteration in the growth properties of tumor cells to explore their contribution in modulation of tumor. Physical exercise of tumor-bearing host resulted in a decreased angiogenesis in the vicinity of tumor. This was also found to be accompanied by a decrease in erythrocyte count and increase in the level of oxygen while the content of lactate showed a concomitant decrease in the tumor microenvironment along with normalization of pH. Moreover, physical exercise also resulted in an inhibition of VEGF expression which was correlated to an altered expression of cytokines: IL-1, IL-4, IL-10, TGF-beta and IFN-gamma. Ascitic fluid of tumor-bearing host subjected to physical exercise showed an increase in nitric oxide content along with an increase in the expression of inducible nitric oxide synthase (iNOS). The study discusses the possible role of the aforesaid alterations in constituents of tumor microenvironment of tumor-bearing host following physical exercise in retardation of tumor growth.