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

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.

Expression of osteopontin and CDX2: Indications of phenotypes and prognosis in advanced gastric cancer

“…Clearly, molecular binding to the cell adhesion molecules integrin and CD44 (4,22) and depletion of growth factors and cytokines (23) could be involved. Of prime importance, however, is the link with prognosis revealed by the present study, in line with the association with malignancy reported earlier (5,24,25).…”

“…Osteopontin (OPN), a 34 kDa extracellular matrix glycophosphoprotein with a cellbinding domain, plays multifunctional roles in cell adhesion, chemotaxis, macrophage-dependent angiogenesis, prevention of apoptosis, and anchorage-independent growth of tumor cells. Its activity regulates cell-matrix interactions and cellular signaling through binding to integrin and CD44 receptors (4)(5)(6). It has been widely reported to demonstrate altered expression in relation to tumorigenesis, invasion, metastasis and its expression may have prognostic potential in colon (7), lung (8), prostate (9), and breast cancers (10).…”

Osteopontin is not Critical for Otoconia Formation or Balance Function

“…The potential impact (if any) of OPN on the CNS and PNS to affect balance and coordination likely involve both positive and negative effects. At the cellular level, the protein has proadhesive, chemotactic and cytokine-like properties, and is involved in a number of physiologic and pathologic events including angiogenesis, apoptosis, inflammation, oxidative stress, remyelination, wound healing, bone remodeling, cell migration and tumorigenesis (Chakraborty et al 2006;El-Tanani et al 2006;Pagano and Haurani 2006). As some of these events lead to neurodegeneration (Maetzler et al 2007;Wung et al 2007) whereas others to neuroprotection (Meller et al 2005;Schroeter et al 2006), the overall outcome in sensorimotor neurons may have been neutralized in the null deletion.…”

CD44v7 ligation downregulates the inflammatory immune response in Crohn's disease patients by apoptosis induction in mononuclear cells from the lamina propria

“…Significance **Po0.01. Control: control IgG; aCD44v7 : anti-CD44v7 antibody 25 What is the evidence for a specific CD44v7 involvement in the inflamed mucosa in CD patients? Apoptotic signaling generally proceeds through the extrinsic and intrinsic pathways.…”