Possible mechanism by which stress accelerates growth of virally derived tumors.

Abstract

Stress accelerates the growth of certain types of tumors. Here we report a possible metabolic mechanism underlying this phenomenon. Some early features of transformation include increased number of glucose transporters and greatly enhanced rates of glucose uptake; this adaptation accommodates the vast energy demands needed for neoplastic growth. In contrast, glucocorticoids, a class of steroid hormones secreted during stress, inhibit glucose transport in various tissues; this is one route by which circulating glucose concentrations are raised during stress. We reasoned that should transformed cells become resistant to this inhibitory action of glucocorticoids, such cells would gain preferential access to these elevated concentrations of glucose. In agreement with this, we observed that Fujinami sarcoma virustransformed fibroblasts became resistant to this glucocorticoid action both in vitro and in the rat. As a result, under conditions where glucocorticoids exerted catabolic effects upon nontransformed fibroblasts (inhibition of metabolism and ATP concentrations), the opposite occurred in the virally transformed cells. We observe that this glucocorticoid resistance upon transformation cannot be explained by depletion of glucocorticoid receptors; previous studies have suggested that transformation causes an alteration in trafficking of such receptors. Because of this resistance of transformed fibroblasts to the inhibitory effects of glucocorticoids upon glucose transport, glucose stores throughout the body are, in effect, preferentially shunted to such tumors during stress.

Minding the body: Psychotherapy and cancer survival

“…Tumour cells become resistant to the catabolic action of cortisol, which inhibits the uptake of glucose in numerous cell types. In such cases, energy would be preferentially shunted to the tumour, and away from normal cells by cortisol (Romero et al, 1992). Thus, there are a variety of means by which depression-related abnormalities in HPA function could affect the rate of cancer progression.…”

The Light-Addressable Potentiometric Sensor: Principles and Biological Applications

“…These authors concluded that this inhibition was caused by decreased rates of glucose transport and protein synthesis in the cells, which are well established effects of glucocorticoids on fibroblasts. In another study that included microphysiometry, this group discovered that virally transformed fibroblasts were resistant to such metabolic inhibition (60). The authors proposed that stress, which causes the secretion of glucocorticoids, accelerates the growth of some types of tumors by this mechanism.…”

Untitled

“…Glucocorticoids have been implicated in tumor growth, both in animal and in in vitro studies [26,27]. Cortisol may accelerate tumor growth via immunosuppressive actions or effects on metabolic processes [28,29]. When cortisol profiles are affected, dysregulated patterns of immune activity and immune cell trafficking may also emerge [30].…”