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.

A recently-developed semiconductor-based instrument, the silicon microphysiometer, allows for realtime, sensitive quantification of cellular metabolism in small numbers of cultured cells with relative case. This is accomplished by detecting the extrusion into the extracellular space of acidic metabolic products of glycolysis, respiration, and ATP hydrolysis, including lactic acid, CO2, and protons. In the present report, we use microphysiometry to observe that glucocorticoids inhibit metabolic rate (as assessed indirectly by a change in the extracellular acidification rate) in fibroblasts (minimal effective dose of 1 nM of corticosterone), whereas 1 microM each estradiol, progesterone and testosterone failed to do so. We suggest that this inhibition of metabolism is secondary to the well-established inhibition of glucose transport and of protein synthesis in fibroblasts by glucocorticoids.