Lectin Reactivities as Intermediate Biomarkers in Premalignant Colorectal Epithelium英文文献.pdfVIP

Journalof Cellular Biochemistry, Supplement 16C:103-109 (1992) Lectin Reactivities as Intermediate Biomarkers in Premalignant Colorectal Epithelium C. Richard Boland, Maria A. Martin, and Irwin J. Goldstein Departments of Internal Medicine and Biological Chemistry, University of Michigan School of Medicine and Veterans Affairs Medical Center, Ann Arbor, Michigan 48109 Abstract Normal colonic epithelial cells undergo maturation as they traverse the crypt to the lumenalsurface. The bindingof lectinsto goblet cell mucinsand other glycoconjugates changes as the cells migrateand differentiate. Additional stepwise modificationsinglycoconjugate expressionoccur in premalignant and malignant neoplasms that may be detected by lectin bindingstudies. The lectins Dolichos biflorusagglutinin(DBA) andsoybean agglutinin (SBA) havebeendeveloped as markersof differentiationin normal-appearing colonic epithelium. Using a quantitative biometricsystemto scoretissues, reduced levels of lectin binding have been found in rectal tissue from patients with familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer. The lectinAmaranthus caudatus agglutinin (ACA) binds to a cytoplasmic glycoconjugate expressed at the base of the colonic crypt and serves as a possible proliferation marker inthe distal, but not proximal, colon. ACA binding increases in tandem with increased levels of proliferation (using BrdU incorporation) in neoplastic tissues. Binding by the peanut lectin (PNA) occurs late in the adenoma-to-carcinomasequence -in larger adenomas and in cancers -and serves as a marker of advancing neoplasia. Lectins identify the stepwise changes that occur during normal differentiation, proliferationand inadvancing neoplasia. Byselectingthe appropriate probe, biomarkers may be develope