A Structural Analysis of Glycosaminoglycans from Lethal and Nonlethal Breast Cancer Tissues: Toward a Novel Class of Theragnostics for Personalized Medicine in Oncology?

Abstract

Cancer is one of the leading noncommunicable diseases that vastly impacts both developed and developing countries. Truly innovative diagnostics that inform disease susceptibility, prognosis, and/or response to treatment (theragnostics) are seriously needed for global public health and personalized medicine for patients with cancer. This study examined the structure and content of glycosaminoglycans (GAGs) in lethal and nonlethal breast cancer tissues from six patients. The glycosaminoglycan content isolated from tissue containing lethal cancer tumors was approximately twice that of other tissues. Molecular weight analysis showed that glycosaminoglycans from cancerous tissue had a longer weight average chain length by an average of five disaccharide units, an increase of approximately 15%. Dissacharide analysis found differences in sulfation patterns between cancerous and normal tissues, as well as sulfation differences in GAG chains isolated from patients with lethal and nonlethal cancer. Specifically, cancerous tissue showed an increase in sulfation at the ''6S'' position of CS chains and an increase in the levels of the HS disaccharide NSCS. Patients with lethal cancer showed a decrease in HS sulfation, with lower levels of ''6S'' and higher levels of the unsulfated ''0S'' disaccharide. Although these findings come from a limited sample size, they indicate that structural changes in GAGs exist between cancerous and noncancerous tissues and between tissues from patients with highly metastatic cancer and cancer that was successfully treated by chemotherapy. Based on these findings, we hypothesize that (1) there are putative changes in the body's construction of GAGs as tissue becomes cancerous; (2) there may be innate structural person-to-person variations in GAG composition that facilitate the metastasis of tumors in some patients when they develop cancer.

Heparan Sulfate Containing Unsubstituted Glucosamine Residues

“…1), which is consistent with previous reports that GlcA-GlcNH 3 ϩ is expressed in highly malignant breast cancers (27). These two cell lines express high levels of heparanase (Fig.…”

Functionalization of Iron Oxide Magnetic Nanoparticles with the Multivalent Pseudopeptide N6l for Breast Tumor Targeting

“…Using these methods, the results indicated that cancer tissue content 3 times more chondroitin sulfate than normal tissue. In addition, structural analysis of the disaccharides indicated 6O sulfate are 3 times higher in tumor tissue compared with normal tissue [33]. From these data, we can assume, with the support of our previous [27] as well as the present data in vitro, that cell-surface sulfated GAGs are implicated in this binding.…”

Analysis of Total Human Urinary Glycosaminoglycan Disaccharides by Liquid Chromatography–Tandem Mass Spectrometry

“…The current study offers a method that is suffciently sensitive to study changes in urinary GAG levels and compositions resulting from diseases outside of MPS such as inflammatory reactions 48 and cancers. 25 Future studies will be directed at applying the current method to such patients.…”