Chondroitin synthases I, II, III and chondroitin sulfate glucuronyltransferase expression in colorectal cancer

Abstract

Abstract. Glycosaminoglycans undergo significant structural alterations in cancer, namely in terms of their sulfation pattern and hydrodynamic size. Numerous studies have focused on this issue, and have demonstrated that glycosaminoglycans play a crucial role in cancer growth and invasion. However, the majority of the enzymes involved in glycosaminoglycan alterations have yet to be examined in detail. The present study focused on the expression of chondroitin-synthesizing enzymes in colorectal cancer. Specimens from healthy controls and cancer patients were subjected to RT-PCR analysis after RNA isolation, and to Western blotting after sequential extraction. The results indicated that chondroitin polymerizing factor and glucuronyltransferase gradually increased with cancer stage, and were expressed at much higher levels in adenomas compared to adjacent normal tissue. The opposite profile was obtained for chondroitin synthase I. Chondroitin synthase III was present at low levels in all the samples examined; however, its expression was higher in the samples from the cancer patients than in those from the healthy controls. It can therefore be concluded that, among the various factors regulating the structure of glycosaminoglycans in cancer, the differential expression of chondroitin-synthesizing enzymes is of the most significance.

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“…CHSY1 encodes a member of the chondroitin N -acetylgalactosaminyltransferase family, possesses dual glucuronyltransferase and galactosaminyltransferase activity and plays critical roles in the biosynthesis of chondroitin sulphate, a glycosaminoglycan involved in many biological processes, including cell proliferation and morphogenesis [24-26]. CHSY1 was one of the significant genes in cluster D and was enriched and regulated by miR-124a.…”

Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic character

“…The expression of all except CHPF were found to decrease in the group of non-metastatic tumors analyzed, while in metastatic CRCs, CHPF alone appeared overexpressed. In previous studies of CRCs, a number of changes have been described: a gradual increase in chondroitin polymerizing factor with advancing cancer stage; an increase in CHSY1 expression in normal tissue adjacent to benign tumors compared to tumoral tissues and high expression levels during the early stages; and low expression levels of CHSY3 in both normal and tumor specimens, although it must be stressed that these studies involved colorectal cancers from different locations and not only right sided CRCs [ 72 ].…”

Genome-wide association study identifies two new susceptibility loci for colorectal cancer at 5q23.3 and 17q12 in Han Chinese

“…It has been reported that co-expression of CHSY3 with CHPF confers a chondroitin sulfate polymerization activity, and chondroitin sulfate plays an important role in cancer biology [ 24 ]. CHSY3 is generally expressed at insignificant levels, but is higher in colorectal tumor cells compared to healthy tissues [ 25 ]. Intriguingly, an eQTL study demonstrated that rs10035791 influenced the expression of cell division cycle 42 small effector 2 ( CDC42SE2 ) in T cells [ 19 ], and a number of SNPs (moderately correlated with rs12522693) have been reported to be associated with the expression of CDC42SE2 in lymphoblastoid cell lines and monocytes [ 26 , 27 ].…”