Extra-Lysosomal Localization of Arylsulfatase B in Human Colonic Epithelium |
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Authors: | Sanjiv V. Prabhu Sumit Bhattacharyya Grace Guzman-Hartman Virgilia Macias Andr�� Kajdacsy-Balla Joanne K. Tobacman |
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Affiliation: | Department of Pathology (SVP,GG-H,VM,AK-B);Department of Medicine (SB,JKT), University of Illinois at Chicago, Chicago, Illinois, and Jesse Brown VA Medical Center, Chicago, Illinois (SB,JKT) |
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Abstract: | The enzyme arylsulfatase B (N-acetylgalactosamine-4-sulfatase; ARSB; ASB) removes 4-sulfate groups from the sulfated glycosaminoglycans (sGAG) chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). Inborn deficiency of ARSB leads to the lysosomal storage disease mucopolysaccharidosis VI, characterized by accumulation of sGAG in vital organs, disruption of normal physiological processes, severe morbidity, and premature death. Recent published work demonstrated extra-lysosomal localization with nuclear and cell membrane ARSB observed in bronchial and colonic epithelial cells, cerebrovascular cells, and hepatic cells. In this report, the authors present ARSB immunostaining in a colonic microarray and show differences in distribution, intensity, and pattern of ARSB staining among normal colon, adenomas, and adenocarcinomas. Distinctive, intense luminal membrane staining was present in the normal epithelial cells but reduced in the malignancies and less in the grade 3 than in the grade 1 adenocarcinomas. In the normal cores, a distinctive pattern of intense cytoplasmic positivity at the luminal surface was followed by reduced staining deeper in the crypts. ARSB enzymatic activity was significantly greater in normal than in malignant tissue. These study findings affirm extra-lysosomal localization of ARSB and suggest that altered ARSB immunostaining and reduced activity may be useful indicators of malignant transformation in human colonic tissue. |
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Keywords: | arylsulfatase B colon adenocarcinoma membrane lysosome chondroitin-4-sulfate |
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