Immunohistochemical expression of heparanase isoforms and syndecan-1 proteins in colorectal adenomas

Abstract

The proteoglycan syndecan-1 and the endoglucuronidases heparanase-1 and heparanase-2 are involved in molecular pathways that deregulate cell adhesion during carcinogenesis. Few studies have examined the expression of syndecan-1, heparanase-1 and mainly heparanase-2 proteins in non-neoplastic and neoplastic human colorectal adenoma tissues. The aim of this study was to analyze the correlation among the heparanase isoforms and the syndecan-1 proteins through immunohistochemical expression in the tissue of colorectal adenomas. Primary antihuman polyclonal anti-HPSE and anti-HPSE2 antibodies and primary anti-human monoclonal anti-SDC1 antibody were used in the immunohistochemical study. The expressions of heparanase-1 and heparanase-2 proteins were determined in tissue samples from 65 colorectal adenomas; the expression of syndecan-1 protein was obtained from 39 (60%) patients. The histological type of adenoma was tubular in 44 (67.7%) patients and tubular-villous in 21 (32.3%); there were no villous adenomas. The polyps were <1.0 cm in size in 54 (83.1%) patients and ≥1.0 cm in 11 (16.9%). The images were quantified by digital counter with a computer program for this purpose. The expression index represented the relationship between the intensity expression and the percentage of positively stained cells. The results showed that the average of heparanase-1, heparanase-2 and syndecan-1 expression index was 73.29 o.u./µm², 93.34 o.u./µm², and 55.29 o.u./µm², respectively. The correlation between the heparanase-1 and syndecan-1 expression index was positive (R=0.034) and significant (P=0.035). There was a negative (R= -0.384) and significant (P=0.016) correlation between the expression index of heparanase-1 and heparanase-2. A negative (R= -0.421) and significant (P=0.008) correlation between the expression index of heparanase-2 and syndecan-1 was found. We concluded that in colorectal adenomas, the heparanase-1 does not participate in syndecan-1 degradation; the heparanase-2 does not stimulate syndecan-1 degradation by the action of heparanase-1, and the heparanase-2 may be involved in the modulation of the heparanase-1 activity.

Extracellular matrix changes in colorectal carcinoma and correlation with lymph node metastasis

“…The present investigation results indicated that HS proteoglycan SYND1 has higher protein and mRNA expression in tumor tissues than non-neoplastic tissues. Such a result was also observed in our group's previous study, which found a significant decrease in CRC tissue's SYND1 protein level than the non-neoplastic colorectal tissue [37]. It is important to note that such studies compared samples from tumor tissues and tissues of patients not affected by neoplasia.…”

“…In contrast, the HPSE gene and protein were already expressed at the colon adenoma stage, which was also observed in the present study [27]. In our previous study, the immunohistochemical analysis revealed a negative correlation between HPSE and HPSE2 proteins in colorectal adenomas [37]. However, the present results clearly showed an increased protein level of both HPSE and HPSE2 in CRC samples compared to adjacent tissues.…”

“…Our group previous studies showed a direct correlation between HPSE and SYND1, whereas we observed an inverse correlation between HPSE2 and HPSE and between HPSE2 and SYND1 in the colorectal adenomas [37]. We also observed an increased HPSE2 protein level and a decreased SYND1 level in CRC [2].…”

Heparanase overexpression down-regulates syndecan-1 expression in a gallbladder carcinoma cell line

“…Therefore, up-regulation of heparanase expression led to down-regulation of syndecan-1, consistent with the results of other studies. 31 , 32 , 9 …”

Salvianolic acid B attenuates renal interstitial fibrosis by regulating the HPSE/SDC1 axis

“…Heparan sulfate (HS) proteoglycans are important constituents of the cell membrane, and they act as co-receptors for cellular signaling. cell surface HS proteoglycans are important regulators of cellular migratory, mitogenic, secretory and inflammatory activities (11). Syndecan-1 (SDC1) is a member of the syndecan family, which comprises a transmembrane HS proteoglycan.…”