Abstract
Our previously published data link P-selectin-reactive chondroitin sulfate structures on the surface of breast cancer cells to metastatic behavior of cells. We have shown that a particular sulfation pattern mediated by the expression of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with P-selectin binding and aggressiveness of human breast cancer cell lines. The present study was performed to evaluate the prognostic value of CHST11 expression and determine whether aberrant DNA methylation controls CHST11 expression in breast cancer. Publicly available datasets were used to examine the association of CHST11 expression to aggressiveness and progression of breast cancer. Methylation status was analyzed using bisulfite genomic sequencing. 5-aza-2′-deoxycytidine (5AzadC) was used for DNA demethylation. Reduced representation bisulfite sequencing was performed in the CpG island of CHST11 with a minimum coverage of 10. Quantitative real-time RT-PCR was employed to confirm the expression profile of CHST11 in breast cancer cell lines. Flow cytometry was also used to confirm the expression of the CHST11 product, chondroitin sulfate A (CS-A). The expression of CHST11 was significantly higher in basal-like and Her2-amplified cell lines compared to luminal cell lines. CHST11 was also highly expressed in cancer tissues compared to normal tissues and the expression levels were significantly associated with tumor progression. We observed very low levels of DNA methylation in a CpG island of CHST11 in basal-like cells but very high levels in the same region in luminal cells. Treatment of MCF7 cells, a luminal cell line with very low expression of CHST11, with 5AzadC increased the expression of CHST11 and its immediate product, CS-A, in a dose-dependent manner. These results suggest that CHST11 may play a direct role in progression of breast cancer and that its expression is controlled by DNA methylation. Therefore, in addition to CHST11 mRNA levels, the methylation status of this gene also has potential as a prognostic biomarker.
Highlights
Increased expression and alteration in sulfation pattern of chondroitin sulfate glycosaminoglycans (CS-GAGs) are observed in various neoplastic tissues, including pancreatic, lung, ovarian and breast [1,2,3]
We have shown that the expression of CHST11 is upregulated in tumor tissues of breast cancer patients compared to their normal tissues and that the expression levels of the gene in breast cancer cell lines correlate with chondroitin sulfate A (CS-A) expression, P-selectin binding and aggressive phenotype [14]
The comparison showed average increases of 2-3.6-fold in CHST11 expression in breast cancer compared to normal tissue
Summary
Increased expression and alteration in sulfation pattern of chondroitin sulfate glycosaminoglycans (CS-GAGs) are observed in various neoplastic tissues, including pancreatic, lung, ovarian and breast [1,2,3]. Several studies, including ours, suggest involvement of particular CS chains in tumor progression and metastasis [2,4,5,6,7]. CHST11 is a key enzyme in the biosynthesis of chondroitin sulfates (CS) and its action on chondroitin chains can lead to the production of chondroitin sulfate A (CS-A), B (CS-B) and E (CS-E) [12,13]. The clinical significance of CHST11 expression is yet to be established and more studies are needed to evaluate the expression of this gene in relation to cancer progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
