Increased LDL receptor mRNA expression in colon cancer is correlated with a rise in plasma cholesterol levels after curative surgery

Abstract

It is currently under debate whether the low serum cholesterol levels that are frequently observed in cancer patients represent a risk factor for/or, rather, are a consequence of the tumour. We postulate that malignant tumours are directly involved in an increased catabolism of cholesterol-rich low-density lipoprotein (LDL) particles. In a prospective study of 25 patients with colorectal carcinoma, we measured intraindividual shifts in serum cholesterol levels after surgery, and the expression of LDL-receptor mRNA in surgically removed specimens. A significant rise in plasma cholesterol levels was observed in patients 3 and 12 months after curative surgery, but not after non-curative surgery. In human colon carcinoma tissues LDL receptor mRNA expression, as determined by competitive reverse-transcriptase-polymerase-chain reaction, was found to be significantly increased when compared to tissues from the tumour-free margin (median values, 1.2 x 10(6) vs. 2.0 x 10(5) molecules/micrograms total cellular RNA, respectively, n = 17). The extent of 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 provides in vivo evidence that the tumour tissue itself contributes to decreased 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 malignancy.

Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for glioblastoma multiforme

“…Increased LDL requirement and receptor activity has been observed in colon cancer (Niendorf et al, 1995), prostate tumors (Chen and Hughes-Fulford, 2001), adrenal tumors (Nakagawa et al, 1995), hormone unresponsive breast tumors (Stranzl et al, 1997), cancers of gynecological origin (Gal et al, 1981), lung tumor tissues (Vitols et al, 1992), leukemia (Tatidis et al, 2002, Vitols et al, 1994, Vitols et al, 1984, Ho et al, 1978, and malignant brain tumors (Rudling et al, 1990). It was previously suggested that plasma-derived LDL could be used as a drug delivery system for tumors expressing LDLR since its hydrophobic core has the possibility of incorporating lipophilic drugs (Firestone, 1994, Rensen et al, 2001.…”

3-Hydroxy-3-methylglutaryl coenzyme A reductase activity and low-density lipoprotein receptor expression in diffuse-type and intestinal-type human gastric cancer

“…14 Moreover, in the present study, the levels of LDLR protein were higher than the levels found in colorectal tumors, 17 in which the role of LDLR and its mRNA in colonic neoplastic growth has been extensively investigated. 17,[22][23][24][25] However, the distribution of LDLR in various normal human tissues and some solid tumors shows considerable variability. 12 Interestingly, among human tumors, only gastric carcinoma has higher 125 LDL binding than other tumors.…”

Tumour enhancement with newly developed Mn-metalloporphyrin (HOP-9P) in magnetic resonance imaging of mice

“…Third, some metalloporphyrin derivatives have high affinity for low-density lipoprotein (LDL), and the uptake is dependent on the lipophilic feature of them. It is generally accepted that in neoplastic cells, LDL receptor distribution is markedly increased (Dagan et al, 1995;Niendorf et al, 1995). Lipophilic porphyrins may be taken into the cancer cells via LDL receptor pathways (Fiel et al, 1988;Kessel et al, 1983;Nakajima et al, 1995;Reyftmann et al, 1984;Takemura et al, 1994).…”