Osteopontin b and c Splice isoforms in Leukemias and Solid Tumors: Angiogenesis Alongside Chemoresistance

Abstract

Osteopontin (OPN) is a glycoprotein involved in regulation of various influences on tumor progression, such as<br />cellular proliferation, apoptosis, angiogenesis, and metastasis. Vascular endothelial growth factor (VEGF) is a secreted<br />molecule supporting angiogenesis in various cancers through activation of the PI3K/AKT/ERK1/2 pathway. OPN and<br />VEGF have a number of isoforms with various activities. In spite of the well-defined association between OPN and<br />VEGF isoform expression and cure rate for solid tumors, there is a scarcity of information as to any association in<br />leukemia. Based on the critical role of OPN in cell survival, it seems reasonable to hypothesize that OPN and VEGF<br />isoform expression levels may impact on chemoresistance and relapse in leukemia the same as in solid tumors. Hence,<br />the aim of our review was to explain relationships between OPN and VEGF isoforms and angiogenesis and related<br />pathways in chemoresistance of leukemia and solid tumors. Our findings demonstrated that OPNb and OPNc alongside<br />with VEGF isoforms and other gene pathways are involved in angiogenesis and also might promote chemoresistance<br />and even recurrence in leukemia and solid tumors. To sum up, targeting OPN isoforms, particularly b and c, might be<br />a novel therapeutic strategy for the treatment of leukemia as well as solid tumors.