Bhattacharyya Sumit, Tobacman Joanne K
Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Clin Exp Metastasis. 2009;26(6):535-45. doi: 10.1007/s10585-009-9253-z. Epub 2009 Mar 22.
Arylsulfatase B (ASB; N-acetylgalactosamine-4-sulfatase; 4-sulfatase; ARSB) is the enzyme that removes 4-sulfate groups from N-acetylgalactosamine 4-sulfate, which combines with glucuronate to form the disaccharide unit of chondroitin-4-sulfate (C4S). In this study, we report how variation in expression of ASB affected the migration of human colonic epithelial cells. In the T84 cell line, derived from lung metastasis of malignant colonic epithelial cells, the activity of ASB, as well as steroid sulfatase, arylsulfatase A, and galactose-6-sulfatase, were significantly less than in normal, primary colonic epithelial cells and in the NCM460 cell line which was derived from normal colonocytes. In the T84 cells, matrix metalloproteinase 9 (MMP9), activated RhoA, and cell migration, as well as C4S content, were significantly more than in the NCM460 cells. Silencing and overexpression of ASB had inverse effects on MMP9, activated RhoA, and cell migration, as well as the C4S content, in the NCM460 and T84 cells. When ASB expression was silenced by siRNA in the NCM460 cells, MMP9 secretion increased to over 3 times the basal level, activated RhoA increased * 85%, and cell migration increased * 52%. Following overexpression of ASB, MMP9 declined 51%, activated RhoA declined * 51%, and cell migration decreased * 37%. These findings demonstrate marked effects of ASB expression on the migratory activity of colonic epithelial cells, activated RhoA, and MMP9, and suggest a potential vital role of ASB, due to its impact on chondroitin sulfation, on determination of the invasive phenotype of colonic epithelial cells.
芳基硫酸酯酶B（ASB；N - 乙酰半乳糖胺 - 4 - 硫酸酯酶；4 - 硫酸酯酶；ARSB）是一种能从N - 乙酰半乳糖胺4 - 硫酸酯上去除4 - 硫酸基团的酶，该基团与葡萄糖醛酸结合形成硫酸软骨素 - 4 - 硫酸酯（C4S）的二糖单位。在本研究中，我们报告了ASB表达的变化如何影响人结肠上皮细胞的迁移。在源自恶性结肠上皮细胞肺转移的T84细胞系中，ASB以及类固醇硫酸酯酶、芳基硫酸酯酶A和半乳糖 - 6 - 硫酸酯酶的活性显著低于正常原代结肠上皮细胞和源自正常结肠细胞的NCM4
60细胞系。在T84细胞中，基质金属蛋白酶9（MMP9）、活化的RhoA、细胞迁移以及C4S含量均显著高于NCM460细胞。ASB的沉默和过表达对NCM460和T84细胞中的MMP9、活化的RhoA、细胞迁移以及C4S含量产生相反的影响。当在NCM460细胞中通过小干扰RNA（siRNA）使ASB表达沉默时，MMP9分泌增加至基础水平的3倍以上，活化的RhoA增加85%，细胞迁移增加52%。ASB过表达后，MMP9下降51%，活化的RhoA下降51%，细胞迁移减少37%。这些发现表明ASB表达对结肠上皮细胞的迁移活性、活化的RhoA和MMP9有显著影响，并提示ASB由于其对硫酸软骨素硫酸化的影响，在决定结肠上皮细胞侵袭表型方面可能具有重要作用。
