Angiogenesis, the formation of new blood vessels from existing vasculature, is fundamental for a variety of physiological and pathological processes including tumor growth andmetastasis. Amsong these factors, vascular endothelial growth factor (VEGF) and transforming growth factor- β1 (TGF-β1) are preeminent glioblastoma-associated multifunctional cytokines that stimulate migration, tissue invasion and angiogenesis.
VEGF is a secreted heparin-binding glycoprotein and one of the most potent endothelial cell-specific mitogens. It is known to play a key role in tumor angiogenesis. TGF-β1 overexpression has been associated with several cancers and correlates with tumor progression, angiogenesis and poor prognosis.
IL-20, an anti-angiogenic cytokine that inhibits COX-2 expressions
Non-small cell lung cancer (NSC LC) cells frequently constitutively overexpress cyclooxy genase-2 (COX -2), a key enzyme in prostaglandins biosynthesis. Because COX-2 overexpression and subsequent prostaglandin-E2(PGE2) production have been implicated inconferring the malignant and metastatic phenotypes, investigations have focused on delineating the mechanisms mediating tumor COX-2 overexpression. Tumor promoters, mutations, cytokines, and growth factors have been shown to induce COX-2 and PGE2 production. IL-10 has the capacity to down-regulate COX-2 in cells such as monocytes. In contrast, IL-10-mediated regulation of COX-2 is not operative in NSCLC. Thus, although IL-10 is the predominant Th2 cytokine in the lung cancer microenvironment, it does not function to control tumor-COX-2 expression. A family of IL-10-related cytokines with limited primary sequence identity but sharing structural homology to IL-10 has been identified. Among these cytokines is IL-20, an anti-angiogenic cytokine. Receptors mediating IL-20 cellular responses have been detected in normal lung tissue. However, this anti-angiogenic cytokine biological function in the pulmonary microenvironment is still un-known. It is the first time that IL -20 inhibits COX- 2/PGE2 production in HBEC and to a lesser degree in NSCLC, and limits COX- 2-mediated angiogenesis is in vitro. Reduced IL-20 expression and efficiency of IL-20 to regulate COX-2/PGE2 in NSCLC cells may thus contribute to maintenance of elevated COX- 2/PGE2 and promotion of tumor angiogenesis.
IFN-γ acts as anti-angiogenic cytokine in the human cornea
Inflammatory processes within the cornea are known to be associated with corneal neovascularization (CN). Corneal avascularity, regulated by VEGF-A and sVEGF-R1 (sFlt-1), primarily contributes to transparency. In addition, IFN-γ, TNF-α, IL-1 a, IL-1 β, and TGF-β were detected in epithelial and stromal cell layers in neovascularized human cornea. TNF-α and IL-1 induced VEGF-A secretion by corneal fibroblasts (HCRF) and this was inhibited significantly by IFN-γ which acts as anti-angiogenic cytokine cytokines.
Angiogenic cytokines related reference
1, Napoleone Ferrara, et al.The biology of VEGF and its receptor.
2,Vijay K. Kommineni, et al. IFN-γ acts as anti-angiogenic cytokine in the human cornea by regulating
the expression of VEGF-A and sVEGF-R1.V.K. Kommineni et al. / Biochemical and Biophysical Research Communications 374 (2008) 479–484
3, Nathalie Heuze´ -Vourc'h, et al. IL-20, an anti-angiogenic cytokine that inhibits
COX-2 expression.Biochemical and Biophysical Research Communications 333 (2005) 470–475