Proangiogenic Role of Tumor–Activated Hepatic Stellate Cells in Experimental Melanoma Metastasis

• DOI: 10.1053/jhep.2003.50068
• Publication Date: 2003-03-15T12:29:29Z
• Authors: Elvira Olaso; Clarisa Salado; Eider Egilegor; Virginia Gutierrez; Aitor Santisteban; Pau Sancho-Bru; Scott L. Friedman; Fernando Vidal-Va...
• Keywords: Hepatic stellate cell; Hepatic tumor

Myofibroblasts infiltrate malignant liver tumors, although their pathogenic implications are unclear. Immunohistochemical detection of α–smooth muscle actin, glial fibrillary acidic protein (GFAP), and CD31 CD34 expression was used to analyze the contribution myofibroblasts angiogenesis in hepatic metastasis produced by intrasplenically–injected B16 melanoma (B16M). Because activated stellate cells (HSCs) oxygen–sensing producing vascular endothelial growth factor (VEGF), effect B16M human A375 supernatants on VEGF production immortalized rat HSC line T6 primary cultured HSCs also studied under an hypoxic atmosphere mimicking a tumor microenvironment. Myofibroblast infiltration preceded endothelium recruitment avascular micrometastasis generated specific stroma for sinusoidal–type portal–type angiogeneses. Thereafter, colocalized within both angiogenic patterns numerical densities correlated with development. often were GFAP–positive, suggesting origin. Melanoma stimulated messenger RNA synthesis HSCs. These effects potentiated hypoxia. up–regulation accompanied increased cyclooxygenase type 2 (COX–2) PGE2 synthesis. decreased COX–2 inhibition, whereas it exogenous PGE2. The high induced factors hypoxia resulted mitogenic, antiapoptotic, motogenic stimulation murine sinusoidal umbilical vein endothelium. In conclusion, temporal positional relationships evolve between myofibroblast during Mechanistically, induction tumor–activated may create proangiogenic microenvironment, facilitating cell survival transition from stage.