The Multifaceted Roles of Osteopontin in Cell Signaling, Tumor Progression and Angiogenesis

Goutam      Chakraborty; Shalini      Jain; Reeti      Behera; Mansoor      Ahmed; Priyanka      Sharma; Vinit      Kumar; Gopal   C.   Kundu

doi:10.2174/156652406779010803

Abstract

Osteopontin (OPN) is a chemokine like phosphorylated glycoprotein that plays important role in cancer progression. Extensive research from various laboratories has demonstrated the likely role of OPN in regulating the cell signaling that ultimately controls tumor growth and metastasis. Several earlier reports indicated that OPN is associated with various cancers; but its functional role in carcinogenesis is still not well defined. Besides the role of OPN in tumor biology, several studies have demonstrated the pathophysiological role of OPN in diverse biological events. This review will focus on recent advances in understanding the molecular mechanism by which OPN regulates a series of signaling cascades through activation of various kinases and transcription factors that ultimately control the expression of downstream effector genes, which contribute to tumor progression and angiogenesis in vitro and animal models. We will also provide evidences that suggest the enhanced expression of OPN is not only associated with several tumor types, but its level of expression is directly correlated to various stages of the clinical specimens of breast and prostate cancers. These studies may be useful for identifying novel OPN-based therapeutic approach for the treatment of cancer.

Keywords: Osteopontin, cell signaling, tumor progression, metastasis, angiogenesis