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 virus-transformed 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.