INCREASED LDL RECEPTOR MESSENGER-RNA EXPRESSION IN COLON-CANCER IS CORRELATED WITH A RISE IN PLASMA-CHOLESTEROL LEVELS AFTER CURATIVE SURGERY

It is currently under debate whether the low serum cholesterol levels that are frequently observed in cancer patients represent a risk facto r for/or, rather, are a consequence of the tumour. We postulate that m alignant tumours are directly involved in an increased catabolism of c holesterol-rich low-density lipoprotein (LDL) particles. In a prospect ive study of 25 patients with colorectal carcinoma, we measured intrai ndividual shifts in serum cholesterol levels after surgery, and the ex pression of LDL-receptor mRNA in surgically removed specimens. A signi ficant rise in plasma cholesterol levels was observed in patients 3 an d 12 months after curative surgery, but not after non-curative surgery . In human colon carcinoma tissues LDL receptor mRNA expression, as de termined by competitive reverse-transcriptase-polymerase-chain reactio n, was found to be significantly increased when compared to tissues fr om the tumour-free margin (median values, 1.2 x 10(6) vs. 2.0 x 10(5) molecules/mu g total cellular RNA, respectively, n = 17). The extent o f LDL-receptor mRNA expression positively correlated to the percentage rise of plasma cholesterol levels 3 months (n = 7, r = 0.8763) and 12 months (n = 6, r = 0.9181) after curative surgery, This finding provi des in vivo evidence that the tumour tissue itself contributes to decr eased plasma cholesterol levels in patients suffering from colorectal carcinomas. It supports the hypothesis that low cholesterol levels in cancer patients are a consequence, and not the cause, of the malignanc y. (C) 1995 Wiley-Liss, Inc.