Effects of norepinephrine or prostaglandin E 2 on extracellular acidification rate of MCG 101, or K1735-M2 tumor cells

Abstract

We studied by microphysiometry functional effects of two different signalling molecules in the murine tumor cell lines, MCG 101 and K1735-M2, namely norepinephrine (NE) and prostaglandin E 2 (PGE 2). This methodology implies estimation of intracellular metabolism by measurents of extracellular acidification rate (ECAR). MCG 101 (an undifferentiated, epithelial-like tumor), in contrast to K1735-M2 (a melanoma), has been found to produce great amounts of PGE 2. Challenge of MCG 101 cells with PGE 2 (0.284 and 2.84 μM for 9 min) elicited an increase in ECAR by about 10 and 41% above basal level, respectively. Pretreatment with indomethacin (0.5 μM) reduced the response to the two PGE 2 concentrations by about 70 and 25%, respectively. In contrast, PGE 2 caused virtually no response in K1735-M2 cells. Moreover, NE caused increases in ECAR in both cell types, possibly via β 3-adrenoceptors, as investigated pharmacologically in MCG 101, and by immunocytochemistry in both cell lines. The results obtained strongly suggest functional receptors for PGE 2 in MCG 101, but not K1735-M2 tumor cells. Functional receptors for NE were demonstrated in both cell lines. There is possibly an autocrine loop in the MCG 101 cells, in which PGE 2 activates cyclooxygenase.