Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma

Sasamura, Hiroto; Takahashi, Atsushi; Miyao, Noriomi; Yanase, Masahiro; Masumori, Naoya; Kitamura, Hiroshi; Itoh, Naoki; Tsukamoto, Taiji

doi:10.1038/sj.bjc.6600152

Cited by 54 publications

(30 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it has been reported that ocular-infiltrating T cells could produce IFN-g 24,25 and IFN-g has been shown to have some antiangiogenic activity through a regulation of the angiogenic factors (eg VEGF, FGF). 22,23 However, in contrast to the theory presented above, another possible mechanism might explain the retinal abnormalities in IL-18 KO mice: endogenous IL-18 might promote vascular network formation, as IL-18 is known to accelerate endothelial cell migration and tube formation in vitro. 11 Our study revealed expanding areas of nonperfusion in IL-18 KO mouse retinas at P14 (Figure 2c and d).…”

Section: Discussionmentioning

confidence: 42%

See 1 more Smart Citation

Abnormal retinal vascular development in IL-18 knockout mice

Qiao

Sonoda

Sassa

et al. 2004

Laboratory Investigation

View full text Add to dashboard Cite

Recent studies have indicated that interleukin 18 (IL-18) might act as either an angiogenic or an angiostatic factor, but the true function of this protein in vascular development is unclear. We therefore investigated the role of IL-18 in the formation of retinal vessels. Development of the retinal vasculature was compared in IL-18 knockout (KO) and wild-type (WT) mice at several different time points. The formation of vessels was evaluated using angiography of flat-mounted retinal samples after inoculation with fluorescein dextran. Retinal samples from both groups were also evaluated through histological examinations, and the expression of angiogenic factors was examined using the reverse-transcription-polymerase chain reaction. The capillary retinal vessels in both WT and IL-18 KO mice had reached the peripheral retina by postnatal day (P) 7. However, IL-18 KO mice showed angiectasis and vascular leakage at P7, especially in the mid-peripheral retina. These symptoms were not observed in WT mice at any stage. Histopathological analysis confirmed abnormal vascular formation in IL-18 KO mice at P14. Interestingly, these abnormalities regressed over time and had disappeared by P84. Several angiogenesis-associated factors, including vascular endothelial growth factor (VEGF), basic fibroblastgrowth factor (bFGF), platelet-derived growth factor (PDGF) and pigment epithelium-derived factor (PEDF), were overexpressed in the retinas of IL-18 KO mice compared with those of WT mice at P14. Interferon-c was detected only in WT mouse retinas at P14. These results provide new evidence for the role of IL-18 in retinal vascular development.

show abstract

Section: Discussionmentioning

confidence: 42%

“…IFN-g has been reported to inhibit tumor angiogenesis; [21][22][23] therefore, it might regulate the formation of retinal vessels. IFN-g mRNA was present at low levels in the IL-18 KO mice, even at P14.…”

Section: Discussionmentioning

confidence: 99%

Abnormal retinal vascular development in IL-18 knockout mice

Qiao

Sonoda

Sassa

et al. 2004

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…IFN-a reduces urokinase-type plasminogen activator and plasminogen activator inhibitor-1 activity (135) and significantly inhibits MMP-9 enzymatic activity and protein expression (136). IFN-a and IFN-h treatment also inhibits angiogenesis by down-regulation of bFGF expression (137)(138)(139), but other studies suggest that the action of IFN-a is not mediated by bFGF or VEGF (140)(141)(142).…”

Section: Non-matrix-derived Inhibitors Of Angiogenesismentioning

confidence: 99%

Endogenous Inhibitors of Angiogenesis

2005

View full text Add to dashboard Cite

show abstract

“…Hypoxic conditions were generated by using the BBL GasPak Pouch System (BD Biosciences), as recently described, which reduces oxygen to less than 2%. 23,24 Human umbilical vein ECs (HUVECs) were freshly isolated from human umbilical veins of newborns by collagenase digestion. 25 HUVECs and bovine aortic endothelial cells (BAECs) were cultured in ECGM (PromoCell) containing 10% heat-inactivated FCS and antibiotics.…”

Section: Antibodies Plasmids Growth Factors Drugs Cells and Mediamentioning

confidence: 99%

The BTB-Kelch Protein KLEIP Controls Endothelial Migration and Sprouting Angiogenesis

Nacak

Alajati

Leptien

et al. 2007

Circulation Research

View full text Add to dashboard Cite

Abstract-Sprouting and invasive migration of endothelial cells are important steps of the angiogenic cascade. Vascular endothelial growth factor (VEGF) induces angiogenesis by activating intracellular signal transduction cascades, which regulate endothelial cell morphology and function. BTB-kelch proteins are intracellular proteins that control cellular architecture and cellular functions. The BTB-kelch protein KLEIP has been characterized as an actin-binding protein that interacts with the nucleotide exchange factor ECT2. We report that KLEIP is preferentially expressed in endothelial cells, suggesting that it may play a critical role in controlling the functions of migrating, proliferating, and invading endothelial cells during angiogenesis. KLEIP mRNA level in endothelial cells is strongly regulated by hypoxia which is controlled by hypoxia-inducible factor-1␣. Functional analysis of KLEIP in endothelial cells revealed that it acts as an essential downstream regulator of VEGF-and basic fibroblast growth factor-induced migration and in-gel sprouting angiogenesis. Yet, it is not involved in controlling VEGF-or basic fibroblast growth factor-mediated proliferative responses. The depletion of KLEIP in endothelial cells blunted the VEGF-induced activation of the monomeric GTPase RhoA but did not alter the VEGF-stimulated activation of extracellular signal-regulated kinase 1/2. Moreover, VEGF induced a physical association of KLEIP with the guanine nucleotide-exchange factor ECT2, the depletion of which also blunted VEGF-induced sprouting. We conclude that the BTB-kelch protein KLEIP is a novel regulator of endothelial function during angiogenesis that controls the VEGF-induced activation of Rho GTPases. (Circ Res. 2007;100:1155-1163.)Key Words: BTB-kelch protein KLEIP Ⅲ angiogenesis Ⅲ migration Ⅲ hypoxia Ⅲ G proteins A ngiogenesis, the formation of blood vessels from preexisting ones, is a crucial process during embryonic development and in several pathological conditions. Vascular endothelial growth factor (VEGF) and its receptors are major regulators of endothelial cell (EC) function and angiogenesis. 1 VEGF is upregulated under hypoxic conditions and induces several angiogenesis-related functions in ECs, such as proliferation, migration, and NO release, which are mediated by cascades of intracellular signaling pathways. [2][3][4] Genetic experiments suggest that VEGF receptor Flk-1/KDR signaling is required for proper positioning of hemangioblastic cells from the posterior primitive streak in the yolk sac. 5 Furthermore, cells lacking Flk1/KDR are unable to coalesce to form blood islands, suggesting that Flk1/KDR signaling controls the migration of ECs. 5 The signaling pathways regulating EC migration involve the phosphorylation of p38 mitogen-activated protein kinase and focal adhesion kinase, 6 activation of phosphatidylinositol 3-kinase, 7 as well as the phosphorylation of protein kinase Akt/protein kinase B, 8,9 with subsequent formation of NO by endothelial NO synthase (eNOS). 10 Yet, mechanistically, V...

show abstract

Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma

Cited by 54 publications

References 36 publications

Abnormal retinal vascular development in IL-18 knockout mice

Abnormal retinal vascular development in IL-18 knockout mice

Endogenous Inhibitors of Angiogenesis

The BTB-Kelch Protein KLEIP Controls Endothelial Migration and Sprouting Angiogenesis

Contact Info

Product

Resources

About