口腔鏈球菌與人類口腔癌細胞，白血球，及癌症相關纖維母細胞之交互作用

Abstract

In the particular microenvironment of oral squamous cell carcinoma (OSCC), the orchestra of cancer cells, infiltrating immune cells, certain bacteria (such as Streptococcus anginosus), and stromal fibroblasts (cancer-associated fibroblasts, CAFs) play a symphony of cancer-related inflammation. In oral cancer, the role of CAFs in modulating the cancer-assoicated inflammation remains poorly understood. The CAFs isolated and cultured from oral cancer tissues are characterized with human fibroblast markers. Recombinant human IL-1β activates CAFs in a dose-dependent manner, and the production of IL-6, IL-8 and MCP-1 in supernatant accumulates as the stimulation time increases. Recombinant IL-1β-activated CAFs express increased levels of proinflammtory cytokines (such as IL-6), and chemokines which are associated with cancer progression, and recruitment of monocytes/macrophages (including IL-8, MCP-1, MCP-3, and GM-CSF). Stimulation of OSCC cells and peripheral blood mononuclear cells with S. anginosus induces the factors which activate CAFs in an IL-1-dependent manner. Conditioned media of CAF promote migration of human monocytes, and IL-1β activation enhances the chemotactic effect. Taken together, both the interaction with invaded streptococci as the exogenous stimuli for immune cells and the endogenous property of OSCC cells lead to IL-1 production. Activation of stromal fibroblasts by IL-1 may give rise to tumor-promoting inflammation in oral cancer microenvironment.