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Horvath, J.
Colon cancer cells recruit and activate eosinophils.
Masterstudium; Biochemie und Molekulare Biomedizin; [ Diplomarbeit/Master Thesis (UNI) ] Technische Universität Graz; 2017. pp.55.

Authors Med Uni Graz:: Horvath Julia
Advisor:: Schicho Rudolf
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Abstract:: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and one of the most common causes of cancer-related deaths worldwide. Despite benefits from early screenings, new treatment options are needed. Recent studies suggest that immunotherapy may become a beneficial option for treatment of colorectal cancer in addition to traditional chemotherapy. In previous studies, eosinophils were found in high counts in the tissue and periphery of colonic tumors. Presence of eosinophils in these tumors has also been reported to correlate with longer patient survival. In addition, eosinophils can induce apoptosis and necrosis in cancer cells. In this we could show that supernatant of human colon cancer cells has the capacity to act as a chemoattractant for eosinophils. Migration of eosinophils towards the supernatants also leads to degranulation and induction of apoptosis and necrosis. Additionally, migrating eosinophils produce less reactive oxygen species as compared to eosinophils that migrate towards unconditioned medium. In the supernatants of colon cancer cells, two chemoattractants for eosinophils could be identified. The first, plasminogen activator inhibitor-1 (PAI-1) is normally involved in fibrolysis of blood cloths and known as a predictor for poor clinical outcome in colorectal cancer. We could show that eosinophils migrate dose-dependently towards the factor, which also induces apoptosis and necrosis. The second identified factor is the monocyte chemoattractant protein-1 (MCP-1) which is known to recruit macrophages to the tumor site and which is involved in metastasis and the regulation of the tumor microenvironment. The factor could be identified as a chemoattractant since eosinophils migrated dose-dependently towards the cytokine. Co-culture experiments with eosinophils and colon cancer cell lines showed that presence of eosinophils can have an impact on signal transduction in colon cancer cells, without the need of direct physical contact between these cells.