Cooperation of Indian Hedgehog and Vascular Endothelial Growth Factor in Tumor Angiogenesis and Growth in Human Hepatocellular Carcinomas, an Immunohistochemical Study

摘要

The Hedgehog (Hh) signaling pathway regulates body patterning and organ development during embryogenesis.1'2 Inappropriate reactivation of the Hh pathway has been linked to many human cancers of the skin, brain, lung, breast, liver, pancreas, gastrointestinal tract, and hema-topoietic system.3"11 Hh signaling generally occurs through the interaction of Hh proteins Sonic Hedgehog (Shh), Indian Hedgehog (Hih), and Desert Hedgehog (Dhh) proteins, with their receptor, patched (Ptch). The interaction releases the catalytic inhibition of the G-protein-coupled receptor-like signal transducer smoothened (Smo). Derepression of Smo triggers a cascade activation of the zinc finger transcription factors glioma-associated oncogene (Gli), leading to the transcription of Hh downstream target genes.1'2'12 The outcome of Hh signaling varies according to the target genes including cyclin B, N-myc, snail, VEGF, and bcl-2, which are involved in cell cycle progression, epithelial-mesenchymal transition, signal transduction, angiogenesis, and apoptosis.1'2'12