Tumor microenvironment, metastasis, inflammation, microbiome, carcinoma
The capacity of tumor cells to metastasize into distant organs is dependent on the adopted tumor microenvironment consisting of altered stroma and infiltrating leukocytes. The aim of our research is to elucidate the cellular and molecular mechanisms leading to formation of a tumor microenvironment that promotes metastasis; and to inhibit metastasis by targeting identified pathways.
The main focus of our studies is the tumor microenvironment in tissue-specific metastasis. We analyze the contribution of altered glycosylation, typical for carcinomas, to tissue-specific metastatic spread. We previously showed that cell-cell mediated interactions among metastatic tumor cells; platelets; leukocytes and a locally activated endothelium induce chemokine expression and thereby promote metastasis. The selectin-mediated recruitment monocytic cells have been linked to increased chemokine concentration at metastatic sites. Importantly, local endothelial activation associated with E-selectin expression and increased chemokine production was shown to be essential for an efficient migration of tumor cells through the endothelial cells. The chemokine-driven recruitment of monocytes has been identified as a critical factor for pulmonary metastasis. Therefore, we test the possibility to inhibit blood-borne metastasis by targeting of the identified chemokines. Inflammation is a determining factor of various cancers, including colorectal cancer. We study the effect of microbiota on inflammation and colon tumorigenesis.Publications