IGF-2   

An adjunct to IGF-I in the clinical evaluation of growth hormone-related disorders, insulin-like growth factor II (IGF-II) is a 7.5 kilodalton, 67 amino acid peptide that is thought to mediate some of the actions of growth hormone (GH). IGF-II peptide consists of the A, C and B chains and is structurally homologous to IGF-I and proinsulin. IGF-II is secreted by the liver and other tissues and is postulated to have mitogenic metabolic actions at or near the sites of synthesis; this has been termed the paracrine role of IGF-II. IGF-II also appears in the peripheral circulation, where it circulates primarily in a high molecular weight tertiary complex with IGF-binding protein-3 (IGFBP-3) and acid-labile subunit. A smaller proportion of IGF-II may circulate in association with other IGF-binding proteins. The proportion of unbound IGF-II in the circulation has been estimated at greater than 5%. 

Plasma levels of IGF-II are dependent upon adequate levels of GH and other factors, including adequate nutrition. The actions of IGF-II are mediated by binding to specific cell surface receptors. The function of the type II IGF receptor is not completely defined. IGF-II binds with lower affinity to the IGF-I type receptors and the insulin receptors. These latter receptors may mediate the mitogenic and metabolic actions of IGF-II. 

Although its specific physiologic role has not been defined, it has been postulated that the interplay of IGF-I and IGF-II with the different cell surface receptors and circulating binding proteins modulates tissue growth. Normal postnatal plasma IGF -II levels are assumed to be at maximum levels, since administration of GH does not result in increased IGF-II levels (unlike IGF-I levels, which increase). Postnatal plasma IGF-II levels show a moderate age-related increase throughout childhood and puberty, and there is no significant variability during the day. IGF-II levels decrease in GH deficiency and in malnutrition. IGF-II levels may also decrease exogenous administration of IGF-I. 

IGF-II overexpression is common in cancer and is a tumor marker for various tumor types, particularly those of mesenchymal and epithelial origin. Pre-clinical evidence demonstrates that not only is increased IGF-II symptomatic of cancer but also that IGF-II is tumorigenic and can promote tumor growth through autocrine or paracrine pathways. 

In addition to IGF-II levels having utility in detecting cancer, IGF-II also has prognostic value; elevated IGF-II correlates with poor prognosis and increased risk of anti-cancer drug resistance. IGF-II quantification can be particularly useful in diagnosing non-islet cell tumor hypoglycemia, which is characterized by a molar IGF-II:IGF-I ratio greater than 10.