8516KAWADA

Abstract

Abstract. Insulin-like growth factor-I (IGF- I Solid tumors are composed of tumor cells, as well as the surrounding stroma, including the extracellular matrix, fibroblasts, macrophages and endothelial cells (1). Because the growth of tumor cells is regulated by the stromal cells through their diffusible factors and adhesion (2-5), tumorstromal cell interactions significantly contribute to the development of some carcinomas, such as those of the breast and prostate (6, 7). Many growth factors and cytokines are known to be involved in the regulation of tumor-stromal cell interactions (2, 8). The various lines of evidence have suggested the involvement of the insulin-like growth factor (IGF) axis in prostate cancer development (9, 10). The IGF axis consists of two major ligands (IGF-I and IGF-II), two cell surface receptors (IGF-IR and IGF-IIR), and six binding proteins (IGFBP-1 to 6) that regulate IGF availability to the receptors and a group of IGFBP proteases that cleave IGFBP and modulate the action of IGFs (11-13). IGF-I binds to IGF-IR, and the tyrosine kinase of the cytoplasmic domain of IGF-IR transduces IGF-I signals into cells 721 Correspondence to: Manabu Kawada, Drug Development Unit