fibrin and Mouth-Neoplasms

Oral angiolipomas are exceedingly rare and little is known about their morphological and etiological features. Here, we report two cases of oral angiolipoma and discuss their clinicopathological and immunohistochemical features, focusing on endothelial markers. Both lesions presented mature adipocytes interspersed by small blood vessels containing fibrin thrombi. Immunohistochemical analysis showed numerous mast cells and expression of CD34, vascular endothelial growth factor, intercellular adhesion molecule-1, interferon-γ and interleukin 6 in most endothelial and stromal cells. Mast cell-endothelial cell interaction may be responsible for the reactive or neoplastic origin of the vascular proliferation of these entities.

Topics: Adipocytes; Adult; Angiolipoma; Antigens, CD34; Endothelial Cells; Endothelium, Vascular; Female; Fibrin; Follow-Up Studies; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-6; Male; Mast Cells; Microvessels; Middle Aged; Mouth Neoplasms; Stromal Cells; Thrombosis; Vascular Endothelial Growth Factor A

A number of studies have implicated the fibrin-coagulation-fibrinolysis system in human tumour progression. Interleukin-8 (IL-8) mediates most of the angiogenic activity induced by human oral squamous cell carcinoma (OSCC) cells. We have recently demonstrated that: (1) fibrin is present in association with IL-8 expressing human OSCC cells in vivo and (2) in situ fibrin polymerisation induces a specific, dose and time-dependent upregulation of IL-8 expression from human OSCC cells in vitro. Our present studies extend this observation by demonstrating that in addition to fibrin formed in situ, both fibrin-derived liquid expressates (soluble fibrin) and preformed fibrin clots induced an over eight-fold stimulation of IL-8 expression from human OSCC cells as compared to media controls. IL-8 upregulation by soluble fibrin was dose-dependent. A monoclonal antibody against the N terminal region of the beta chain of human fibrin (Bbeta15-42) inhibited 67% of soluble fibrin-induced IL-8 expression from human OSCC cells. A peptide (GHRP), representing the sequence at the N terminus of this region, induced a dose-dependent stimulation of IL-8 expression, further confirming the role of this region. These studies directly support our hypothesis that fibrin induces protumourigenic factor expression from tumour cells, thus promoting tumour progression. Future studies to further characterise the role of the Bbeta15-42 region in tumour cell activation may lead to the design of peptide antagonists with important therapeutic potential.

Topics: Aged; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-8; Macromolecular Substances; Male; Mouth Neoplasms; Oligopeptides; Peptide Fragments; Structure-Activity Relationship; Tumor Cells, Cultured; Up-Regulation

We have recently demonstrated that fibrin induces a specific, dose- and time-dependent upregulation of the angiogenic factor interleukin 8 (IL-8) from human oral squamous cell carcinoma (OSCC) cells in vitro. In this study we begin to test the hypothesis that fibrin induces IL-8 expression from tumor cells in vivo by studying their in vivo association in OSCC.. The presence of fibrin(ogen) was initially evaluated in 20 archival human OSCCs by means of immunohistochemistry with a polyclonal antibody. The presence of fibrin and IL-8 was then studied in 19 sections from 8 different patients' head and neck tumors (including 6 OSCCs) by means of immunohistochemistry with a monoclonal antibody against fibrin. These 8 tumors had been treated with inhibitors of new fibrin formation and degradation immediately after surgical removal.. Fibrin staining was found in 100% of the tumor sections tested. IL-8 staining was found in the cytoplasm of tumor cells in 100% of the studied tumors, including areas adjacent to fibrin.. These data demonstrate an in vivo association between fibrin and IL-8 in OSCC. These studies support our hypothesis that fibrin induces expression of protumorigenic factors such as IL-8 from tumor cells in vivo.

Topics: Antibodies; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Coloring Agents; Cytoplasm; Fibrin; Fibrinogen; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Interleukin-8; Mouth Neoplasms; Tumor Cells, Cultured; Up-Regulation

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.

Topics: Analysis of Variance; Carcinoma, Squamous Cell; Cell Line; Dose-Response Relationship, Drug; Epithelium; Fibrin; Humans; Interleukin-8; Mouth Mucosa; Mouth Neoplasms; Neoplasm Proteins; Neovascularization, Pathologic; Pharyngeal Neoplasms; Stimulation, Chemical; Time Factors; Tumor Cells, Cultured

Topics: Adenoma; Carcinoma; Culture Media; Culture Techniques; Cyclohexanecarboxylic Acids; Fibrin; Fibrinogen; Fibrinolysis; Fibroma; Granuloma; Granuloma, Giant Cell; Hemangioma; Humans; Methylamines; Mouth Neoplasms; Neoplasms, Muscle Tissue