Interactions of CFTR and Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) in Prostate Carcinoma.

Defective CFTR (cystic fibrosis transmembrane conductance regulator) is pathognomonic for cystic fibrosis (CF), which is characterized by an accumulation of tenacious secretions in pulmonary airways, as well as by abnormal ductal secretions in other organs, including the pancreas and prostate. The advent of CFTR modulating therapies has markedly improved the clinical status and survival of CF patients, primarily attributable to improved lung function. Previous publications reported that a decline in CFTR function was associated with a decline in activity and expression of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB). ARSB removes 4-sulfate groups from N-acetylgalactosamine 4-sulfate residues and is required for the degradation of chondroitin 4-sulfate (chondroitin sulfate A) and dermatan sulfate, two sulfated glycosaminoglycans which accumulate in cystic fibrosis. Declines in both ARSB and in CFTR have been associated with the development of malignancies, including prostate malignancy. The experiments in this report show that similar effects on invasiveness are present when either CFTR or ARSB is inhibited in human prostate epithelial cells, and these effects resemble findings detected in malignant prostate tissue. The effects of CFTR inhibition are reversed by treatment with recombinant human ARSB in prostate cells. These results suggest that treatment by rhARSB may benefit patients with cystic fibrosis and prostate cancer.