Study of escape mechanism from host immunity by cancer-derived cytokine

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In this research project, the investigator aimed to elucidate the mechanism that cancer cells escape from the host immunity to promote cancer progression. The target of the project is focused on RAGE-HMGB1/amphoterin system, because the investigator already characterized the metastasis-related features of the system. The results of the project showed that HMGB1/amphoterin secreted from cancer cells induces apoptosis by activating RAGE in the macrophages. Colon cancer cases with HMGB1/amphoterin overexpression showed macrophage-negative areas in the cancer tissues. The macrophage depletion is significantly associated with metastasis and poor prognosis of disease.The RAGE-HMGB1/amphoterin system is employed to colon carcinogenesis. In the AOM-induced rat colon cancer model, overexpression of RAGE and secretion of HMGB1/amphoterin are observed from the early stage of epithelial cell transformation. Transplanted tumors of human colon cancer cells in nude mice are suppressed by direct injection of an HMGB1/amphoterin-neutralizing antibody into the tumors accompanied with increase of tumor-associated macrophages.These results overall indicate that the RAGE-HMGB1/amphoterin system plays a pivotal role in colon cancer development, progression, and metastasis by suppression of the host anti-cancer immunity in addition to activation of cancer cell invasion. It suggests that the RAGE-HMGB1/amphoterin system is an important target of cancer treatment.