Survivin in cancer diagnosis and therapy - a review

Abstract

Survivin in cancer diagnosis and therapya reviewFailure of cancer treatment mainly results from metastasis formation and to a certain extent from local neoplastic infiltration. Numerous genes coding for growth factors and their receptors, adhesion proteins, and cell cycle regulatory proteins are involved in the process of carcinogenesis. Cancer microenvironment is characterized by uncontrolled production of growth factors and cytokines. In tumor specimens, an increased synthesis of the epidermal growth factor (EGF), vascular epidermal growth factor (VEGF), fibroblast growth factor (FBF), insulin-like growth factor (IGF), and various cytokines (e.g. TGF, IL-1, IL-8) have been found (1,2). Protein overexpression leads to the escape of cancer cells from apoptosis and to autonomic signal transduction stimulating tumor growth, angiogenesis, and eventually metastasis formation.Caspases, a group of cysteine proteases are involved in apoptosis. The proteins are initiated through different entry sites, such as mitochondria (mitochondrial pathway) and death receptors (receptor pathway); the latter begins with the activation of the TNF receptor that reacts with caspase-8-activating Fadd/Mort-1 protein and forms the DISC complex, which then transduces apoptotic signals and activates caspase-3 (Fig. 1).The mitochondrial pathway of apoptosis is initiated with cytochrom c release from mitochondria, which normally is localized between an inner and outer mitochodrial membrane. Factors like UVirradiation and chemotherapy stimulate cytochrome c release into the cytosol; there it reacts with Apaf-1 protein and dATP forming an apoptosome activating pro-caspase-9, followed by caspase-3 activation and finally by cell death.The third way of apoptotic protein activation is based on caspase-3 activation by granzyme В (serine protease). Caspase-3 links together those three ways of apoptosis induction; activated caspase-3 mediates cleavage of intracellular proteins leading to cell death (Fig. 1).Mitochondrial and receptor pathways are strictly connected. They are involved in BID protein activation; the protein belongs to the family of Bcl-2 proapoptotic proteins. BID is cleaved and activated by caspase-8 (mitochondrial pathway), and then migrates to mitochondria stimulating cytochrome c release (receptor pathway). Granzyme В also activates BID in the process of proteolysis, and induces apoptosis.

Expression and Function of Survivin in Canine Osteosarcoma

“…Survivin expression has prognostic significance in many types of human cancer (26). Small studies in human osteosarcoma have suggested that survivin may be useful in determining prognosis and degree of malignancy (27)(28)(29); however, definitive studies about the role of survivin in human osteosarcoma are lacking.…”