Phosphatidylcholine (PC), a glycerophospholipid bearing a polar phosphocholine head group and two non-polar fatty acid hydrocarbon chains, represents the main membrane-forming phospholipid in mammalian cells. Removal of one of the fatty acids, enzymatically or by spontaneous hydrolysis, results in lyso-phosphatidylcholine (LPC). In contrast to PC, which is a membrane forming phospholipid, LPC exerts a lytic action on membranes . In living cells, LPC usually results from membrane PC through the enzymatic action of a phospholipase A2 (PLA2), which cleaves the fatty acid from the 2-position of the glycerol backbone. In the blood, LPC is usually generated by PLA2 or by the lecithin-cholesterol-acyl-transferase (LCAT) from PC present in lipoproteins. The latter enzyme transfers a fatty acid from PC to cholesterol, resulting in a cholesterolester and LPC . It has been reported that triglyceride lipases on endothelial cells are also able to generate LPC by cleaving the fatty acid ester bond in the 1 position of glycerophospholipids in lipoproteins . Since LPC is membrane lytic, it is predominantly bound to albumin in the blood and the amount of free, monomolecular dissolved LPC which is in equilibrium with albumin-bound LPC – is very small. However, even though the equilibrium is shifted strongly towards albumin-bound LPC, LPC transfer into cells seems to be fast. It can be taken up by cells rapidly and LPC released into the blood from membrane PC is quickly bound to albumin. Thus, the albumin system keeps LPC concentrations in the blood below the lytic concentration but at the same time provides rapid supply if necessary.
The concentration of LPC in blood plasma of healthy persons usually ranges from 200 to 300 μM [4, 5]. Our own unpublished observations confirmed this range. Sullentrop et al. as well as Kuliszkiewicz-Janus et al. have reported slightly higher ranges of LPC for healthy persons, varying between 300 and 400 μM [6, 7].
It has been observed that ras-transformed cell lines have a higher PC-turnover and a higher consumption of LPC than normal cells . Elevated pools of two PC breakdown products, phosphocholine and glycerophosphocholine, were observed in these experiments . It has been reported that the ras oncogene product directly or indirectly causes an increased turnover of PC in mouse fibroblast cells . Another study indicated that PC hydrolysis is a target of Ras during the transduction of growth factor-initiated mitogenic signals .
In correspondence to the finding that tumour cells consume more LPC than normal cells, patients with malignant diseases have been found to show changes of the usual plasma phospholipid pattern. The analysis of plasma lipids in a group of patients with different kinds of cancer revealed a general decrease of phospholipids . A group of patients with leukemia, malignant lymphomas as well as gastrointestinal and renal tumours was found to have decreased LPC concentrations even at an early stage of disease compared to healthy persons . In patients with acute leukemia significantly diminished plasma LPC concentrations normalised with treatment induced disease remission . Similar results were observed in patients with renal cancer. In comparison with healthy volunteers, both male and female patients had decreased LPC concentrations in plasma which could be related to tumour status and metastasis .
Based on these findings, we postulated that decreased plasma LPC concentrations might be a general indicator for malignant disease and may even allow a predication of the state of disease. We, therefore, examined the LPC concentrations in a group of 59 cancer patients with different disease entities and varying stages of disease progression. We determined inflammatory parameters as well as the nutritional status, since severity of disease is generally associated with an activation of systemic inflammatory processes and a deterioration of nutritional status .