Characterization of malignant colon tumors with31p nuclear magnetic resonance phospholipid and phosphatic metabolite profiles

Abstract

Background. To further characterize selected pathologic features on a biochemical level, the authors analyzed the nuclear magnetic resonance metabolite and phospholipid spectra of 30 malignant colon tumors using 31P magnetic resonance spectroscopy. Methods. Eleven individual generic phospholipids were identified in the spectra of 17 phospholipid extracts, and 31 individual phosphatic metabolites were identified in the spectra of 13 perchloric acid extracts. The metabolites and lipids were quantified for statistical intergroup comparisons based on tumor stage, lymph node status, differentiation, mucin production, blood vessel invasion (BVI), and lymphatic vessel invasion (LVI). Results. Significant elevations in the relative concentration of α‐glycerol phosphate were noted when comparing AJCC tumor classification (T3 vs. T2, 0.92 ± 0.14 vs. 0.46 ± 0.11, P < 0.009), tumor differentiation (moderately vs. well differentiated, 0.92 ± 0.14 vs. 0.46 ± 0.11, P < 0.009), and BVI (presence vs. absence, 1.03 ± 0.04 vs. 0.68 ± 0.10, P < 0.028) by elastic tissue stain. Among the tissue phospholipids analyzed, the relative concentration of a choline phospholipid was significantly different when comparing moderately and poorly differentiated tumors (6.26 ± 0.56 vs. 3.29 ± 0.30, P < 0.001), T2 and T3 tumors (3.90 ± 0.45 vs. 6.31 ± 0.56, P < 0.009), and mucin‐positive vs. mucin‐negative tumors (4.46 ± 0.56 vs. 6.83 ± 0.76, P < 0.028). Differences in lymph node status of the cases analyzed in this study (lymph node positive vs. lymph node negative) were noted for tumors with elevated levels of sphingomyelin (8.13 ± 0.40 vs. 6.88 ± 0.16, P < 0.02), diminished levels of phosphatidylinositol (5.25 ± 0.27 vs. 6.38 ± 0.34, P < 0.02), elevated levels of beta‐glycerol phosphate (5.30 ± 0.70 vs. 1.20 ± 0.06, P < 0.05), and elevated levels of glycerol 3‐phosphoserine (0.48 ± 0.01 vs. 0.23 ± 0.02, P< 0.002). Conclusions. The characteristic differences in the phospholipid and intermediate phosphate metabolite profiles identified through magnetic resonance spectroscopic and histopathologic analysis may provide important information regarding the nature of tumor and cell membrane metabolism. Differences in these profiles may identify markers useful for biologic behavior, provide prognostic information, and characterize the impact of the pathologic features of colon cancer. Cancer 1995; 76:1715–23.

Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: A key factor to the unrestrained cell proliferation?

“…It has been shown that supplement of SM in the diet to normal mice significantly reduced the number of aberrant crypt foci in the colon and inhibited the development of colon carcinoma induced by chemical carcinogens (Dillehay et al, 1994;Schmelz et al, 1996). In agreement with this, human colonic carcinomas as well as colonic mucosa of rats treated with chemical dimethylhydrazine, show an accumulation of SM (Dudeja et al, 1986;Merchant et al, 1995), which may well be the result of a reduced SMase activity as shown in our previous work (Hertervig et al, 1997). In addition, ursodeoxycholate, a bile salt that has been shown to inhibit experimental colon cancer development (Earnest et al, 1994) has recently been found to increase alkaline SMase activity in rats (Duan et al, 1998).…”

“…Human colonic carcinomas, as well as the colonic mucosa of rats treated with colonic carcinogens, are associated with an accumulation of SM (Dudeja et al, 1986;Merchant et al, 1995). In normal mice, dietary supplement of SM has been shown to reduce the number of aberrant colonic crypt foci (considered to be early biomarkers of dysplastic change in the epithelium) and mice given 1,2-dimethyl-hydrazine, a colonic carcinogen, together with SM, showed an increase in the proportion of adenomas versus adenocarcinomas, indicating a possible chemopreventive role (Dillehay et al, 1994;Schmelz et al, 1996).…”

Molecular mechanisms of drug resistance and its reversal in cancer

“…Similarly, these phospholipids are found in distinctive levels in healthy and cancerous esophagus cells (Merchant et al, 1993). Merchant et al also reported that cholesterol is found in different levels in the cells at different phases of colon cancer (Merchant et al, 1995). Interestingly, there was no difference in the phospholipid composition of healthy and cancerous liver cells, but cholesterol levels are found to be significantly lower in cancerous cells.…”

Prospects of ‘Omics Based Molecular Approaches in Colorectal Cancer Diagnosis and Treatment in the Developing World: A Case Study in Cape Town, South Africa

“…[116] Similarly, elevated profiles of phosphatidylcholine and choline kinase activity have been demonstrated it colon cancers [117] and a high ratio of phosphatidylcholine to phosphatidylethanolamine has been used to differential metastatic colon cancers from localized ones. [118] Elevated levels of sphingomyelin have also been reported to characterize human colon cancer, based on nuclear magnetic resonance (NMR) studies [119], whilst cancer cell motility was shown to be down-regulated by the interaction between CD9 and sialoglycosphingolipid GM3 using CRC cell lines [120] and ceramides have been found to induce apoptosis in CRC cell lines (HT-29, LOVO, and HCT-116). [121][122][123] Urinary phospholipids analysis using nanoflow LC-ESI MS/MS has been previously used for the analysis of breast [124,125]) and prostate cancer [124], but there is a dearth of literature on the application of this method to colorectal cancer.…”