RELEASE OF LIPOPROTEIN-LIPASE FROM EHRLICH ASCITES TUMOR PRODUCED BY AN ASSOCIATION WITH A RAPID INCREASE IN CYCLIC-AMP CONTENT

Although it is considered that the lipoprotein metabolism in tumor pla ys an important role in growth and multiplication, it is not clear as to the details. Lipoprotein lipase (LPL) is a key enzyme responsible f or the hydrolysis of lipoprotein-triacylglyceride. In this study, we e xamined the regulatory step of LPL in lipoprotein metabolism of Ehrlic h ascites tumor and especially the enzyme-release from the tumor cells . When LPL was stimulated to release from the tumor cells by the low m olecular weight dextran sulfate (3.2 kDa), cyclic AMP content in the t umor cells was observed to increase rapidly in a time-dependent manner up to 30 s; its maximal effect was 1.5-fold higher than the basal lev el of cyclic AMP. The increase in cyclic AMP content was more enhanced in the presence of isobutylmethylxanthine and was never suppressed by propranolol. Moreover, cyclic AMP-dependent protein kinase (PKA) acti vity in the tumor cells was also recognized to elevate in a time-and d ose-dependent manner. In addition, the release of LPL activity from th e tumor cells was inhibited by 2',5'-dideoxyadenosine. These results s uggest that LPL in the tumor cells is released through a pathway invol ving an activation of PKA associated with the rapid increase in cyclic AMP content. (C) 1998 Elsevier Science Ireland Ltd.