Expression of chondroitin sulfotransferases (CHST3,7,11,15) and chondroitin sulfatases in normal and malignant prostate stroma and epithelium

Abstract

Previous work demonstrated marked decline in arylsulfatase B (ARSB; N‐acetylgalactosamine‐4‐sulfatase) in malignant prostate tissues by immunohistochemistry, activity assay, and mRNA expression. In contrast, activity of galactosamine‐N‐acetyl‐6‐sulfatase (GALNS; N‐acetylgalactosamine‐6‐sulfatase) was significantly increased in malignant prostate tissues. These findings were associated with marked increase in chondroitin 4‐sulfate (C4S), decline in chondroitin 6‐sulfate (C6S), and increased C4S:C6S ratio in the malignant tissues. To further evaluate the chondroitin sulfation, mRNA expression of chondroitin sulfotransferases and chondroitin sulfatases was detected in malignant and normal prostate stromal and epithelial tissues obtained by laser capture microdissection (LCMD) of prostate tissues obtained from the Biorepository of the University of Illinois at Chicago. Primers were identified using Primer3, and QPCR was used to determine expression levels. Confirmation of epithelial vs. stromal content was confirmed by comparative expression of vimentin and E‐cadherin. ARSB expression was similar in the control and malignant stromal tissue and more than two‐fold higher than in the normal epithelial tissue. ARSB expression was reduced by over 50% in the malignant epithelium compared to normal epithelium. In contrast, GALNS expression was over 50% less in the stromal tissues than in the epithelium, and was increased almost two‐fold in the malignant vs. normal prostate epithelium. The expression of CHST15, which adds a 6‐sulfate group to C4S, was increased over four‐fold in the malignant prostate epithelium, and significantly reduced in both normal and malignant stromal tissue. Expression of the 6‐O sulfotransferases CHST3 and CHST7 was also determined. Normal and malignant stromal CHST3 was about 50% the level in the normal and malignant epithelium. CHST7 was slightly less in the malignant epithelium, compared to the normal epithelium and the normal and malignant stroma. The 4‐O sulfotransferase CHST11 was reduced about 50% in the malignant epithelium, compared to normal epithelium, and increased about 80% in the normal and malignant stroma. These findings suggest that increased expression of CHST15 and GALNS in the epithelium may lead to enhanced production of C4S. This is perhaps compensatory, due to decline in CHST11. However, in association with decline in ARSB, these effects lead to increased epithelial C4S. Since increased C4S has been associated with reduced activity of SHP2, the tyrosine‐protein phosphatase non‐receptor type 11 (PTPN11) and increased availability of galectin‐3, these changes have important consequences for cell signaling, growth, and metabolism and for stromal‐epithelial interactions.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.