VEGF gene alternative splicing: pro- and anti-angiogenic isoforms in cancer

Abstract

Tumor growth and progression depend on angiogenesis, a process of new blood vessels formation from a preexisting vascular endothelium. Tumors promote angiogenesis by secreting or activating angiogenic factors that stimulate endothelial proliferation and migration and capillary morphogenesis. The newly formed blood vessels provide nutrients and oxygen to the tumor, increasing its growth. Thus, angiogenesis plays a key role in cancer progression and development of metastases. An important growth factor that promotes angiogenesis and participates in a variety of physiological and pathological processes is the vascular endothelial growth factor (VEGF-A or VEGF). Overexpression of VEGF results in increased angiogenesis in normal and pathological conditions. The existence of an alternative site of splicing at the 3' untranslated region of the mRNA results in the expression of isoforms with a C-terminal region which are downregulated in tumors and may have differential inhibitory effects. This suggests that control of splicing can be an important regulatory mechanism of angiogenesis in cancer.

Methodologies in creating skin substitutes

“…However, overexpression of VEGF has been linked to numerous pathologies including several different types of cancers and microvascular complications of diabetes mellitus[100,101]. A few studies have been performed using VEGF to enhance wound healing.…”

Magnetic nanosphere-guided site-specific delivery of vascular endothelial growth factor gene attenuates restenosis in rabbit balloon-injured artery

“…Indeed, it is possible for VEGF level increase in circulation to promote exacerbation of diabetic retinopathy or the development of a tumor currently too small to be recognized. [41][42][43] A strategy to overcome these hurdles is to use VEGF gene uniquely localized at the site of administration. Previous studies have shown that as-prepared magnetic nanoparticles are superparamagnetic.…”

“…These findings are similar to those previously reported for the treatment of an ischemic limb model, in which magnetic nanosphere-guided drugs promoted direct contact of specific tissues and reduced systemic exposure. 42 Moreover, nanoparticles are small enough to be evacuated by the kidneys. Therefore, nanoparticles are superior to a coated stent, with no local exotic existence that disturbs the re-endothelialization of damaged vessel, and finally attenuate restenosis.…”

Splice variants in the proteome: a promising and challenging field to targeted drug discovery

“…Cancer growth is also closely related to the vascular endothelial growth factor A (VEGF-A) gene, which has a key role in angiogenesis. This gene expresses two families of isoform: proangiogenic and antiangiogenic, classified as VEGFxxx and VEGFxxxb, respectively [46]. Consequently, the balance between these two isoforms interferes in cancer development, such as in neuroblastoma, where the antiangiogenic isoform is upregulated at the levels of mRNA and the resulting protein [47].…”