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VEGF-induced Angiogenesis (VEGF-induce + angiogenesi)
Selected AbstractsHyaluronan-binding peptide can inhibit tumor growth by interacting with Bcl-2INTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Ninfei Liu Abstract Previous studies have indicated that proteins that bind hyaluronan can also inhibit the growth of tumor cells. To determine if synthetic peptides also possessed these properties, we tested a series of polypeptides containing structural motifs from different proteins for their ability to bind [3H]hyaluronan, and identified one compound termed P4 that had a particularly strong interaction. Further studies revealed that P4 also inhibited the growth of tumor cells in tissue culture as well as on the chorioallantoic membranes of chicken embryos. In addition, expression vectors for P4 caused tumor cells to grow slower in nude mice and reduced their vascularization. The P4 peptide also inhibited VEGF-induced angiogenesis in the chorioallantoic membranes of chicken embryos. Studies on cultured cells indicated that P4 induced apoptosis, which was blocked by a pan-caspase inhibitor. Confocal microscopy revealed that shortly after its uptake, P4 became associated with mitochondria. Immunoprecipitation indicated that P4 could bind to Bcl-2 and Bcl-xL, which are associated with mitochondria and regulate apoptosis. This was also supported by the fact that P4 induced the release of cytochrome c from preparations of mitochondria. Taken together, these results suggest that P4 binds to Bcl-2 and related proteins and this activates the apoptotic cascade. © 2003 Wiley-Liss, Inc. [source] ABSTRACTS: 1 Implication of soluble receptors of VEGF, sVEGFR-1 and sVEGFR-2, in angiogenesisAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 20082TH -6TH JUNE 2008 TOP SELECTED ABSTRACTS, 4TH EMBIC SUMMER SCHOOL, BARCELONA, SPAIN Introduction:, sVEGFR-1 and sVEGFR-2 are soluble forms of the membrane-bound receptors of VEGF. sVEGFR-1 is detected in plasma of pre-eclamptic women, during ischemia and in some cancer cases. sVEGFR-2, was recently detected in plasma of healthy people, in leukaemia and in systemic erythematosus lupus cases. sVEGFR-1 has anti-angiogenic properties in vitro and in vivo but sVEGFR-2 remains uncharacterized and its physiological or pathological role is still unknown. Material and Methods:, The aim of this study was to understand and to characterize the role of sVEGFR2 in angiogenesis and in endothelial function. Results:, In aortic ring assay, an ex vivo model of angiogenesis, sVEGFR1 and sVEGFR2 were able to abolish VEGF-induced angiogenesis. However, when used alone, they induced the formation of a "network", supposed to be vascular in visible microscopy. As they were able to abolish the effect of VEGF on endothelial function but showed no direct effect alone, we performed an immuno-staining of the "vascular network" induced by the soluble receptors. It showed that there were a few endothelial cells but mostly pericytes/smooth muscle cells (PC/SMC). Our first in vitro experiments on PC/SMC showed that sVEGFR-1 and sVEGFR-2 were able to promote the migration of PC/SMC, only in presence of endothelial cells. Conclusions:, Our results evidence that sVEGFR1 and sVEGFR2 inhibit VEGF-induced angiogenesis in a similar way. However, they have also a direct effect on PC/SMC, promoting their migration. Our results suggest that these soluble receptors could act, not only on endothelial cells themselves, but by a direct effect on PC/SMC too. These results contribute to identify factors by which it could be possible to regulate the balance between pro-angiogenic and anti-angiogenic factors, especially in the case of the anti-VEGF drugs used now as anti-cancer therapies in clinics, where a transient "normalization" of the vessels is observed. [source] Antitumor activities of synthetic and natural stilbenes through antiangiogenic actionCANCER SCIENCE, Issue 10 2008Yoshiyuki Kimura We reported that the antitumor and antimetastatic actions of resveratrol might be due to the inhibition of tumor-induced angiogenesis. To search for anticancer agents with stronger activity than resveratrol, we examined the antiangiogenic effects of 21 synthetic and/or natural stilbenes. Among these 21 stilbenes, 2,3-, 3,4-, and 4,4,-dihydroxystilbene inhibited the pro-matrix metalloproteinase (pro-MMP),9 production in colon 26 cells at 5,25 µM, vascular endothelial growth factor (VEGF),induced human umbilical vein endothelial cell (HUVEC) migration at 10 and 25 µM, and VEGF-induced angiogenesis at 5,50 µM. Resvertarol inhibited the pro-MMP-9 production and VEGF-induced angiogenesis at 25 or 50 µM. Thus, the inhibition of pro-MMP-9 production in colon 26 cells and VEGF-induced angiogenesis by three dihydroxystilbenes were greater than those of resveratrol. The three dihydroxystilbenes (8 mg/kg, intraperitoneal injection) inhibited the tumor-induced neovascularization in colon 26,packed chamber-bearing mice and the tumor growth in colon 26,bearing mice. Furthermore, the three dihydroxystilbenes inhibited VEGF-induced VEGFR-2 phosphorylation. On the other hand, the three dihydroxystilbenes had no effect on VEGFR-1 and-2 expression, and VEGF-induced VEGFR-1 phosphorylation in HUVECs. These findings suggest that the inhibition of tumor-induced neovascularization by these three dihydroxystilbenes may be due to the inhibition of VEGF-induced endothelial cell migration and VEGF-induced angiogenesis through the inhibition of VEGF-induced VEGFR-2 phosphorylation in endothelial cells and pro-MMP-9 expression in colon 26 cells. (Cancer Sci 2008; 99: 2083,2096) [source] Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in human malignant melanoma and their relation to angiogenesisCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2006Y.-T. Tu Summary Background., Angiogenesis is the major and key factor for growth and invasion of tumours, including malignant melanoma (MM), but the factors that contribute to tumour angiogenesis are still unclear., Objective., To study expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in human MM and their relation to angiogenesis. To investigate the correlation between eNOS and VEGF and the role of nitric oxide (NO) generated by eNOS in the process of mediating angiogenesis by VEGF. Methods., Tissue sections from 31 patients with MM were examined using immunohistochemistry and morphological quantitative analysis for protein expression of eNOS and VEGF. Microvessel density (MVD) was counted in endothelial cells in immunostained by anti-FVIII:RAg antibody. Results., Positive eNOS and VEGF immunostaining were observed in 77.4% and 83.9% of MM lesions, respectively, whereas pigmented naevi never expessed eNOS and VEGF. A positive correlation between eNOS and VEGF in MM was observed. Expression of eNOS and VEGF was positively correlated with MVD expression in MM, and MVD expression in MM was stronger than in pigmented naevi. Expression of eNOS and VEGF was not correlated with lymph node metastasis. Conclusions., On the basis of the current data showing that malignant melanocytic tumours displayed strong VEGF and eNOS expression, whereas benign melanocytic proliferations showed no immunoreactivity for VEGF and eNOS, such expression may be used as a discriminating factor to distinguish malignant melanoma from pigmented naevi. Expression of eNOS and VEGF may contribute to angiogenesis of MM, eNOS probably plays an important role in mediating VEGF-induced angiogenesis. [source] | ||||||||||