24 research outputs found

    Significant Role of Collagen XVII And Integrin β4 in Migration and Invasion of The Less Aggressive Squamous Cell Carcinoma Cells

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    Collagen XVII and integrin alpha 6 beta 4 have well-established roles as epithelial adhesion molecules. Their binding partner laminin 332 as well as integrin alpha 6 beta 4 are largely recognized to promote invasion and metastasis in various cancers, and collagen XVII is essential for the survival of colon and lung cancer stem cells. We have studied the expression of laminin.2, collagen XVII and integrin beta 4 in tissue microarray samples of squamous cell carcinoma (SCC) and its precursors, actinic keratosis and Bowen's disease. The expression of laminin.2 was highest in SCC samples, whereas the expression of collagen XVII and integrin beta 4 varied greatly in SCC and its precursors. Collagen XVII and integrin beta 4 were also expressed in SCC cell lines. Virus-mediated RNAi knockdown of collagen XVII and integrin beta 4 reduced the migration of less aggressive SCC-25 cells in horizontal scratch wound healing assay. Additionally, in a 3D organotypic myoma invasion assay the loss of collagen XVII or integrin beta 4 suppressed equally the migration and invasion of SCC-25 cells whereas there was no effect on the most aggressive HSC-3 cells. Variable expression patterns and results in migration and invasion assays suggest that collagen XVII and integrin beta 4 contribute to SCC tumorigenesis

    Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment

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    BACKGROUND: Mismatch repair deficient (dMMR) colorectal cancer (CRC) is associated with a conspicuous local immune infiltrate, however its relationship with systemic inflammatory responses remains to be determined. The present study aims to examine the relationships and prognostic value of assessment of the local and systemic environment in the context of MMR status in patients with CRC. METHODS: The relationship between MMR status, determined using immunohistochemistry, and the local inflammatory cell infiltrate, differential white cell count, neutrophil:platelet score (NPS), neutrophil:lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS), and cancer-specific survival was examined in 228 patients undergoing resection of stage I-III CRC. RESULTS: 35 patients (15%) had dMMR CRC. dMMR was associated with a higher density of CD3+, CD8+, CD45R0+ T-lymphocytes within the cancer cell nests, and an elevated mGPS (mGPS2: 23% vs. 9%, P=0.007) and NPS (NPS2: 19% vs. 3%, P=0.001). CD3+ density (P<0.001), mGPS (P=0.01) and NPS (P=0.042) were associated with survival independent of MMR status (P=0.367) and stratified five-year survival of patients with MMR competent CRC from 94% to 67%, 83% to 46% and 78% to 60% respectively. CONCLUSION: MMR deficiency was associated with local and systemic environments, and compared with their assessment, dMMR had relatively poor prognostic value in patients with primary operable CRC. In addition to MMR status, local and systemic inflammatory responses should be assessed in these patients
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