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

Document Type: Systematic Review and Meta-analysis

Authors

1 Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

2 Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Tehran, Iran.

Abstract

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

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