ABSTRACT
In recent studies, we have demonstrated that fibrin is present in association with tumor cells in oral squamous cell carcinoma (OSCC) in vivo. We hypothesized that this fibrin can directly induce the expression of known angiogenic factors from oral tumor cells. Since IL-8 is known to be the major inducer of angiogenesis caused by these cells, we examined the ability of fibrin to stimulate IL-8 expression from OSCC cells in vitro. A physiologically relevant concentration of fibrin was found to cause a dose and time-dependent stimulation of IL-8 expression from oral and pharyngeal tumor cells but not from a non-tumorigenic oral cell line. Fibrinogen, thrombin and collagen were all unable to induce significant IL-8 expression, establishing the specificity of fibrin in causing this response. Gel filtration chromatography confirmed the molecular identity of the IL-8 antigen detected in the ELISA system used. These results suggest that fibrin may promote angiogenesis in oral tumors in vivo by directly upregulating the expression of IL-8 from tumor cells.
Subject(s)
Carcinoma, Squamous Cell/immunology , Fibrin/pharmacology , Interleukin-8/metabolism , Mouth Neoplasms/immunology , Neoplasm Proteins/metabolism , Analysis of Variance , Carcinoma, Squamous Cell/blood supply , Cell Line , Dose-Response Relationship, Drug , Epithelium , Humans , Interleukin-8/analysis , Mouth Mucosa , Mouth Neoplasms/blood supply , Neoplasm Proteins/analysis , Neovascularization, Pathologic , Pharyngeal Neoplasms/blood supply , Pharyngeal Neoplasms/immunology , Stimulation, Chemical , Time Factors , Tumor Cells, Cultured/drug effectsABSTRACT
Rat lymphocytes obtained from spleens, lymph nodes, and thymus glands showed migratory responses to a variety of factors including fluids from mixed lymphocyte culture fluids from concanavalin A-stimulated cells, fluids from phagocytizing macrophages, and to anti-rat IgG. Migratory responses to the last factor were bimodal over a dose range of anti-Ig; at high concentrations of anti-Ig, the response appeared to be nonspecific, whereas, at low concentrations, the responses seemed to be chemotactic in character. When lymphocytes from spleens, lymph nodes, and thymic glands were compared, qualitative and quantitative differences on the responses were evident with use of the three attractants. When spleen lymphocytes were separated into T cell- and B cell-enriched fractions, T cells responded to the culture fluids from mixed lymphocyte cultures, whereas B cells seemed to respond poorly, if at all. Only B cells responded to anti-Ig. These findings may explain, at least in part, the accumulation of lymphoid cells at sites of inflammatory stimuli.
