Changes in the expression of syndecan-1 in the colorectal adenoma-carcinoma sequence

Syndecan-1, a transmembrane heparan sulphate proteoglycan (HSPG), functions as a matrix receptor on the basal surface of epithelial cells. It also co- localizes with E-cadherin at the lateral cell surface where its function is uncertain. Tumour development in the large bowel is associated with loss o f normal epithelial adhesion and altered patterns of expression of cell adh esion molecules, possibly including syndecan-1. To evaluate changes in synd ecan-1 expression during the development of colorectal neoplasia, 59 adenom as and 20 carcinomas arising from adenomas were investigated by immunohisto chemistry. The staining intensity and distribution of syndecan-1 and E-cadh erin in sequential sections was examined, semi-quantified and compared. Sta ining of syndecan-1 and E-cadherin was uniform in normal colorectal epithel ial cells, and located at the basolateral surface. No significant change wa s seen in either molecule in mildly or moderately dysplastic adenomas. A si gnificant reduction in expression of both syndecan-1 and E-cadherin was see n in severely dysplastic epithelium as compared to moderate dysplasia (P=0. 001 and P=0.004 respectively). Similarly, there was a significant reduction of both molecules in carcinomas compared with associated adenomas (syndeca n-1 P=0.00003; E-cadherin P=0.002). In both cases the loss of syndecan-1 ex pression was more striking than that of E-cadherin. Previous in vitro studi es have shown that epithelial cells made deficient in syndecan-1 cease to e xpress E-cadherin, suggesting a causal association. Our results support the se findings and indicate that disruption of cell-matrix adhesion is critica l in colorectal carcinogenesis, probably preceding changes in the purely ho motypic cell-cell adhesion mediated by E-cadherin.