³¹P NMR spectroscopy of blood plasma: determination and quantification of phospholipid classes in patients with renal cell carcinoma

Abstract

Advanced renal cell carcinoma (RCC) has a poor prognosis and is characterized by an unpredictable clinical course. The aim of this study was to assess the systemic phospholipid distribution as a possible marker of tumor stage and tumor spread beyond the kidney. To this end, the effect of renal cell carcinoma (RCC) on phospholipid concentrations in blood plasma using 31P NMR spectroscopy was studied in: (a) 29 patients with RCC prior to nephrectomy; (b) 19 healthy volunteers; (c) three patients with other renal tumors (renal metastases of bronchial carcinoma and of renal pelvic carcinoma, and a benign renal tumor). Furthermore, the phospholipid concentrations of eight patients of group (a) were determined 6 months after nephrectomy, when they were in remission. We found considerable deviations in the concentrations of the lysophosphatidylcholines (LPC1, LPC2) in both male and female patients with RCC compared to healthy volunteers (male--LPC1 0.217+/-0.062 vs 0.297+/-0.049 mmol/l, LPC2 0.036+/-0.014 vs 0.068+/-0.024 mmol/l; female--LPC1 0.195+/-0.071 vs 0.296+/-0.044 mmol/l, LPC2 0.037+/-0.027 vs 0.044+/-0.014 mmol/l). In addition, female patients with RCC showed lower concentrations of phosphatidylcholines (PC; 1.409+/-0.268 vs 1.947+/-0.259 mmol/l). The low phospholipid concentrations normalized for patients in remission. Phospholipid concentrations were found to depend on tumor stage and metastatic spread. The deviations in phospholipid concentrations (LPC1, LPC2, PC) observed may be attributable to systemic effects caused by the tumor as well as changes in enzyme activities.

Lysophosphatidylcholine Pretreatment Reduces VLA-4 and P-Selectin–Mediated B16.F10 Melanoma Cell Adhesion In vitro and Inhibits Metastasis-Like Lung Invasion In vivo

“…This has also been observed in other tumor cells (Jantscheff et al, unpublished data) and this effect can be discussed as one possible cause for the strongly reduced LysoPC plasma amounts observed in patients with advanced metastatic cancer (17)(18)(19)(20)(21). In addition, a radical shift in tumor cell membrane FA composition toward saturated FAs was observed, culminating between 48 and 72 hours without increasing after further LysoPC exposure (Fig.…”

“…The inhibitory effects of LysoPC on B16.F10 cell adhesion were observed after approximately 48 to 72 hours at a threshold concentration of 400 mmol/L or greater, slightly higher than physiologic human plasma levels (200-400 mmol/L; refs. [16][17][18], and were remarkably intensified by repeated application of LysoPC. Because exposure to LysoPC concentration above the threshold did not alter expression levels of VLA-4 and P-selectin or binding to soluble structures (Fig.…”

“…The FA composition of plasma LysoPC in healthy individuals is comparable with that of total plasma PL; our unpublished studies confirm that more than 31% of the plasma LysoPC molecules carry unsaturated FAs. Various clinical observations have shown that plasma LysoPC levels are often decreased in advanced metastatic cancer patients (17)(18)(19)(20), especially when weight loss and inflammatory processes occur (21). This finding suggests a deregulation of the aforementioned LysoPC balance by malignant tumors and clearly indicates the potential importance of LysoPC in metastatic and cachectic processes.…”

“…These enzymes mostly hydrolyze lipoprotein-associated PL, both at the SN À1 as well as the SN À2 position (11)(12)(13)(14)(15)(16), thereby contributing to a pool of LysoPL that represents about one tenth of the total amount of plasma PL (9). The concentration of LysoPC was found to be constant in blood plasma of healthy persons, ranging from 200 to 300 mmol/L (16) or 300 to 400 mmol/L (17,18), suggesting a sensitive balance between generation and removal of LysoPC (e.g., by cellular uptake). The FA composition of plasma LysoPC in healthy individuals is comparable with that of total plasma PL; our unpublished studies confirm that more than 31% of the plasma LysoPC molecules carry unsaturated FAs.…”

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabolic profiling of human serum prior to and following radical resection of colorectal carcinoma

“…LPCs act as a bioactive mediator in various biological processes, including injury and inflammatory responses (29,30), cellular motility, growth and regulation of differentiation (31). Numerous clinical experiments have shown that serum LPCs levels are lower in patients with advanced cancer (32)(33)(34). However, the results of the present study also showed that LPCs containing saturated fatty acids were upregulated in CRC patients.…”