**1. Introduction**

The insulin-like growth factor (IGF) system comprises of ligands IGF-I, IGF-II, its corresponding cell-membrane receptors IGF-I receptor (IGF-IR), IGF-II receptor (IGF-IIR), IGF-binding proteins (IGFBPs), and IGFBP degrading enzymes known as proteases. The IGF system plays a critical role in somatic growth in an endocrine fashion as well as cell proliferation, survival, and di fferentiation of normal and malignant cells in a paracrine/autocrine fashion. Dysregulation of the IGF system attributes to pathophysiology of a variety of human diseases such as cancer, diabetes, chronic inflammatory disease, and malnutrition. In particular, IGF/IGF-IR-independent actions of IGFBP-3 have been extensively investigated and their involvement in initiation and progression of various cancers has been recognized.
