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Chronic colitis is associated with a reduction of mucosal alkaline sphingomyelinase activity
Urban Sjöqvist1, Erik Hertervig, Ake Nilsson
1Division of Gastroenterology, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. urban.sjoqvist@sos.sll.se
Background And Aims:
The hydrolysis of sphingomyelin (SM) generates key molecules regulating cell growth. Animal cancer studies support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. The activity of a specific intestinal alkaline sphingomyelinase (SMase), which hydrolyzes SM, is reduced in colorectal tumors. In this study we measured alkaline SMase activity in patients with longstanding colitis and assessed if a reduction can be used as a marker in surveillance of high risk patients.
Methods:
Alkaline SMase activity was measured in 139 colonic biopsies from 34 patients with longstanding, extensive colitis and from 11 controls. Fifteen patients had earlier diagnosis of dysplasia or DNA aneuploidy. Alkaline SMase activity was related to histologic dysplasia and DNA aneuploidy assessed by flow cytometry, patient age, and duration of disease.
Results:
Alkaline SMase activity was significantly lower in the patient group with and without dysplasia compared with controls (p = 0.006). In biopsies, an association was not found between alkaline SMase activity, dysplasia, or DNA ploidy. However, alkaline SMase activity decreased with age both in patients and controls (p = 0.008).
Conclusions:
Reduction of alkaline SMase activity seen in colorectal cancer and adenomas is also present in patients with chronic colitis. It is not complementary to dysplasia or DNA-aneuploidy in the identification of high risk patients. The age-associated decrease of alkaline SMase activity seems to be a general phenomenon indicating premature senescence of the mucosa in longstanding colitis.
Insights
Reduced intestinal alkaline sphingomyelinase (SMase) activity, observed in colorectal tumors, is also present in patients with chronic colitis. This reduction is not a marker for high-risk patients but may indicate premature mucosal senescence with age.
Area of Science:
- Gastroenterology
- Molecular Biology
- Oncology
Background:
- Sphingomyelin (SM) hydrolysis by alkaline sphingomyelinase (SMase) yields molecules that regulate cell growth.
- Reduced SMase activity is linked to colorectal tumors, suggesting a protective role in colonic mucosa.
- Intestinal SMase activity is diminished in colorectal cancer and adenomas.
Purpose of the Study:
- To measure alkaline SMase activity in patients with longstanding colitis.
- To determine if reduced SMase activity can serve as a surveillance marker for high-risk individuals.
- To investigate the association between SMase activity, dysplasia, and DNA aneuploidy.
Main Methods:
- Alkaline SMase activity was quantified in 139 colonic biopsies from 34 colitis patients and 11 controls.
- Histologic dysplasia and DNA aneuploidy (via flow cytometry) were assessed.
- SMase activity was correlated with dysplasia, DNA ploidy, patient age, and disease duration.
Main Results:
- Alkaline SMase activity was significantly lower in colitis patients compared to controls (p=0.006).
- No association was found between SMase activity and dysplasia or DNA ploidy in biopsies.
- SMase activity demonstrated an age-dependent decrease in both patients and controls (p=0.008).
Conclusions:
- Reduced alkaline SMase activity, a feature of colorectal cancer, is also present in chronic colitis.
- SMase activity reduction is not a complementary marker for identifying high-risk patients with dysplasia or DNA aneuploidy.
- The age-related decline in SMase activity suggests premature mucosal senescence in longstanding colitis.