| Summary: | The tumor microenvironment is important for tumor growth and progression, where the cancer associated fibroblast (CAF) is one central cell type. The CpG island methylator phenotype (CIMP) divides colorectal cancer (CRC) into three subgroups and in this study we investigate how the different CIMP-groups and adjacent fibroblasts affect each other. This was done with the aim of finding CIMP-specific markers and to see if different tumor-fibroblast interactions result in differently invasive tumors. Here we report that CIMP-negative tumors have increased expression of fibronectin, while CIMP-high tumors have reduced expression of E-cadherin, findings that were seen in both tumor tissue samples and tumor cell lines. We also show that CIMP-negative and CIMP-high cancer cells induce an alignment of the fibronectin fibers produced by the fibroblasts and that CIMP-high cancer cells migrate with directionality on these matrices. These findings indicate that the different tumor subgroups in fact induce different phenotypes in CAFs, resulting in CIMP-specific markers. They also indicate that CIMP-negative and CIMP-high tumors may induce an alignment of fibronectin in order to promote cancer cell migration and thereby also tumor invasion.
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