Reduced Expression of Syndecan‐1 Affects Metastatic Potential and Clinical Outcome in Patients with Colorectal Cancer

Syndecan‐1 is a transmembrane heparansulfate proteoglycan which regulates cell‐to‐cell or cell‐to‐extracellular matrix interactions and may influence malignant cell behavior. We investigated the alterations of syndecan‐1 expressions in colorectal cancers and analyzed the relationship between histological and clinical characteristics. Syndecan‐1 protein expression in colorectal cancer tissues was investigated with immunohistochemical staining of resected specimens. In situ hybridization was performed using syndecan‐1 riboprobe to confirm the transcriptional signals. Syndecan‐1 mRNA expression in cancer cell lines cultured with or without methylation inhibitor was also analyzed by quantitative PCR. Out of 105 specimens tested, less than 25% of tumor cells were stained with anti‐syndecan‐1 monoclonal antibody in 36 (34.3%). In situ hybridization showed a similar staining profile to that of immunohistochemistry. Syndecan‐1 mRNA expression was increased by the methylation inhibitor 5‐aza‐2′‐deoxycytidine, suggesting that the hypermethylation is involved in the suppression of syndecan‐1 expression. Clinically, the incidence of metastasis to lymphnode or liver in patients with syndecan‐1‐negative tumors was significantly high. Among Tl colorectal cancers displaying a primary invasive phase, lymphnode metastasis, undifferentiated characters and ‘budding’ of cancer cells were more common in syndecan‐1‐negative tumors. The survival rate in patients with syndecan‐1‐negative tumors was decreased significantly in a stage‐independent manner. These results suggest that the reduction of syndecan‐1 expression in colorectal cancer cells, which is supposed to be regulated at the transcription level, is closely related to invasive character. The evaluation of syndecan‐1 expression in colorectal cancer may allow prediction of patients' survival after surgery