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

Abstract

[...]synthesis of chondroitin sulfate showed some alterations, which affected various steps, including polimerization and the modification of chains, but the main variations dependent on the presence of metastases were epimerization and 6C sulfation; however, when compared with RSCRCs, the essential divergences affected polymerization of the chains and the 6C sulfation of the galactosamine residue. Since function ultimately relies on the fine structure of the chains, cells exercise accurate control over HSPG composition and sequence, which results in these molecules varying depending on factors like cell type and development stage, as well as due to pathological processes. The results from the qRT-PCR analysis identified transcripts of these genes in both metastatic and non-metastatic tumors as well as in normal tissue (Fig. 1a and b), although there were no significant differences in their transcript levels (Fig. 1c). qRT-PCR analysis of serglycin, a cell-associated PG which is intracellular [23], unlike other HSPGs, showed decreased levels, around 35% of the values obtained for healthy tissues, independent of the metastatic nature of the tumor (Fig. 1), and affecting 70–75% of the samples analyzed (p < 0.05). Since serglycin is principally located in mast cell secretory granules [23], we were prompted to attempt to detect these cells through immunohistochemical studies using the antibody CD117. [...]the synthesis of the CS chains showed differences with respect to the RSCRCs which preferentially affected the polymerization of the chains and the 6C sulfation of the GalNAc residue.