These results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.

No abstract

Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer. This mechanism is frequently associated with the impairment of either E-cadherin expression or function. However, mechanisms of such abnormalities have not been fully elucidated. In this study, we demonstrated that the function of E-cadherin was completely abolished in the human gastric cancer cell line HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins, ␤-catenin. Although immunofluorescence staining of HSC-39 cells by using an anti-E-cadherin antibody (HECD-1) revealed the strong and uniform expression of E-cadherin on the cell surface, cell compaction and cell aggregation were not observed in this cell. Western blotting (immunoblotting) using HECD-1 exhibited a 120-kDa band which is equivalent to normal E-cadherin. Northern (RNA) blotting demonstrated a 4.7-kb band, the same as mature E-cadherin mRNA. Immunoprecipitation of metabolically labeled proteins with HECD-1 revealed three bands corresponding to E-cadherin, ␣-catenin, and ␥-catenin and a 79-kDa band which was apparently smaller than that of normal ␤-catenin, indicating truncated ␤-catenin. The 79-kDa band was immunologically identified as ␤-catenin by using immunoblotting with anti-␤-catenin antibodies. Examination of ␤-catenin mRNA by the reverse transcriptase-PCR method revealed a transcript which was shorter than that of normal ␤-catenin. The sequencing of PCR product for ␤-catenin confirmed deletion in 321 bases from nucleotides ؉82 to ؉402. Southern blotting of ␤-catenin DNA disclosed mutation at the genomic level. Expression vectors of ␤-catenin were introduced into HSC-39 cells by transfection. In the obtained transfectants, E-cadherin-dependent cell-cell adhesiveness was recovered, as revealed by cell compaction, cell aggregation, and immunofluorescence staining. From these results, it was concluded that in HSC-39 cells, impaired cell-cell adhesion is due to mutations in ␤-catenin which results in the dysfunction of E-cadherin.

No abstract

Although stromal cell-derived factor (SDF)-1a and its receptor CXCR4 are experimentally suggested to be involved in tumorigenicity, the clinicopathological significance of their expression in human disease is not fully understood. We examined SDF-1a and CXCR4 expression in colorectal cancers (CRCs) and their related lymph nodes (LNs), and investigated its relationship to clinicopathological features. Specimens of 60 primary CRCs and 27 related LNs were examined immunohistochemically for not only positivity but also immunostaining patterns for SDF-1a and CXCR4. The relationships between clinicopathological features and SDF-1a or CXCR4 expression were then analysed. Stromal cell-derived factor-1a and CXCR4 expression were significantly associated with LN metastasis, tumour stage, and survival of CRC patients. Twenty-nine of 47 CXCR4-positive CRCs (61.7%) showed clear CXCR4 immunoreactivity in the nucleus and a weak signal in the cytoplasm (nuclear type), whereas others showed no nuclear immunoreactivity but a diffuse signal in the cytoplasm and at the plasma membrane (cytomembrane type). Colorectal cancer patients with nuclear CXCR4 expression showed significantly more frequent LN metastasis than did those with cytomembrane expression. Colorectal cancer patients with nuclear CXCR4 expression in the primary lesion frequently had cytomembrane CXCR4-positive tumours in their LNs. In conclusion, expression of SDF-1a and nuclear CXCR4 predicts LN metastasis in CRCs.