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Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: a key
E Hertervig1, A Nilsson, J Björk
1Department of Medicine, Lund University Hospital, Sweden.
British Journal of Cancer
|September 25, 1999
Summary
Reduced alkaline sphingomyelinase activity in the colon may promote cancer development. This study found significantly lower enzyme levels in precancerous polyps and surrounding tissue, suggesting a role in colorectal neoplasia.
Area of Science:
- Biochemistry
- Oncology
- Gastroenterology
Background:
- Sphingomyelin hydrolysis yields molecules crucial for cell growth and apoptosis.
- Animal models suggest this pathway inhibits colonic malignant transformation.
- Alkaline sphingomyelinase activity is reduced in colorectal adenocarcinomas.
Purpose of the Study:
- To investigate sphingomyelinase activity in premalignant colorectal lesions.
- To determine if reduced sphingomyelinase levels precede neoplastic transformation.
- To assess enzyme activity in familial adenomatous polyposis (FAP) and sporadic adenomas.
Main Methods:
- Measured acid, neutral, and alkaline sphingomyelinase activities in tissue samples.
- Analyzed adenomas and surrounding mucosa from FAP patients, sporadic adenoma patients, and controls.
- Assessed alkaline phosphatase activity as a comparative marker.
Main Results:
- Alkaline sphingomyelinase activity was significantly reduced (90%) in FAP adenomas and surrounding mucosa.
- Acid (66%) and neutral (54%) sphingomyelinase activities were also reduced in FAP adenomas.
- Sporadic adenomas showed a significant reduction (57%) in alkaline sphingomyelinase activity.
Conclusions:
- Markedly reduced alkaline sphingomyelinase activity in FAP adenomas and mucosa may drive unrestrained cell proliferation.
- This deficiency could be a pathogenic factor in colorectal neoplastic transformation.
- Sphingomyelinase levels are altered even in the premalignant state of colorectal cancer.