Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma

Abstract

perimental colon carcinoma in mice, indicating that the abnormal metabolism of sphingomyelin is linked to colon carcinoma development. However, the changes 1 Department of Medicine, Lund University Hospital, Lund, Sweden.in sphingomyelinase (SMase) activity in colon carcinoma have not been directly studied. The authors identified, specifically in the intestine, a distinctive alkaline 2 Research Park Ideon, Swedish Dairies AssociSMase that differs from the known acidic and neutral SMases. The functions and ation, Lund, Sweden.clinical implications of the enzyme are unknown. This study examined the changes 3 Department of Cell Biology, Lund University in all three SMase activities in human colorectal carcinoma. Hospital; Lund, Sweden. METHODS.Tissue samples were taken from colorectal carcinoma and normal mucosa from 18 patients. After homogenization, the activities of acidic, neutral, and alkaline SMase, as well as ceramidase and alkaline phosphatase, were determined. The enzyme activities in cancer tissue were compared with normal tissue from the same patients. RESULTS.In the normal tissue, there is an activity gradient from the ascending colon to the rectum for neutral and alkaline SMases but not for acidic SMase. In colorectal carcinoma, alkaline SMase activity was preferentially decreased by 75%, whereas acidic and neutral SMase activity decreased by 30% and 50%, respectively. No changes could be found for either ceramidase or alkaline phosphatase activity. CONCLUSIONS.Alkaline SMase activity preferentially decreases in human colorectal carcinoma, suggesting a regulatory role of the enzyme in colon mucosa cell proliferation.

Chronic Colitis Is Associated With a Reduction of Mucosal Alkaline Sphingomyelinase Activity

“…In previous studies we found reduced alkaline SMase activity in sporadic colorectal adenomas, in colorectal carcinomas, and in patients with familial adenomatous polyposis both in adenomas and flat mucosa (10,11).…”

“…DNA ploidy measurement is therefore used as another objective marker for malignant transformation at some centers. Alkaline SMase activity has previously been found to be reduced by 50% in colorectal adenomas, by 75% in colorectal cancer, and by 90% in the adenomas and flat mucosa of familial adenomatous polyposis patients (10,11). Furthermore, ursodeoxycholate, which has been shown to be preventive in experimental colorectal carcinogenesis (25), has been found to increase alkaline SMase activity in colorectal mucosa (26).…”

Rapid screening of specific changes in mRNA in thyroid carcinomas by sequence specific-differential display: Decreased expression of acid ceramidase mRNA in malignant and benign thyroid tumors

“…Only a few studies have reported on the presence of ceramide and ceramidase in cancer tissues. In human colorectal carcinoma, according to Hertervig et al (1997), cellular levels of ceramide are low due to decreased sphingomyelinase activity, and ceramidase activity is not altered. In the present study, levels of AC mRNA were decreased in thyroid tumor tissues, especially in anaplastic carcinomas, suggesting decreased AC activity in these tissues.…”

Modulation of signal transduction in cancer cells by phytosterols

“…Experimental evidence indicates that activation of alkaline sphingomyelinase in the human colon functions as an antiproliferative pathway through its generation of ceramides [31]. Reduction in alkaline sphingomyelinase activity has been reported in human colon cancers and mutations in the enzyme exist in transformed human colon cancer cell lines [32, 33].…”