The role of VEGF and thrombospondins in skin angiogenesis

Detmar, Michael

doi:10.1016/s0923-1811(00)00145-6

Cited by 156 publications

(137 citation statements)

References 27 publications

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“…Its extracellular domain contains five repeats with putative antiangiogenic function as they are highly homologous to TSRs. TSRs are properdin type repeats initially found in TSP-1, an extracellular matrix glycoprotein, which was the first identified naturally occurring angiogenesis inhibitor (Lawler and Hynes, 1986;Good et al, 1990;Detmar, 2000;de Fraipont et al, 2001). TSP-1 directly binds to endothelial cells and inhibits their migration and proliferation ( its antiangiogenic activity has been mapped to two of its three TSRs.…”

Section: Discussionmentioning

confidence: 99%

“…TSP-1 directly interacts with endothelial cells through binding of its TSRs to CD36, a cell surface receptor. This binding then activates a signaling cascade that results in increased FasL expression leading to induction of apoptosis in endothelial cells (Dawson et al, 1997;Detmar, 2000;Jimenez et al, 2000;Volpert et al, 2002b;Simantov and Silverstein, 2003). TSP-1 also contains an RGD integrin binding motif and integrin ligation by RGD is thought to contribute to endothelial growth inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…TSP-1 also contains an RGD integrin binding motif and integrin ligation by RGD is thought to contribute to endothelial growth inhibition. Furthermore, an RFK sequence within the second TSR in TSP-1 activates TGF-b, which can inhibit endothelial cell growth (Muller et al, 1987;Detmar, 2000). Based on the number and position of conserved cysteines, the TSRs in BAI1 belong to group A type I TSP repeats, similar to TSP-1 TSRs (Huwiler et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Vasculostatin, a proteolytic fragment of Brain Angiogenesis Inhibitor 1, is an antiangiogenic and antitumorigenic factor

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Vasculostatin, a proteolytic fragment of Brain Angiogenesis Inhibitor 1, is an antiangiogenic and antitumorigenic factor

et al. 2005

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“…NMSC is one of the most common malignancies in humans: basal cell carcinomas and SCCs represent the vast majority of the tumors diagnosed (Limmer, 2001). NMSC are believed to arise from stem cells of the hair follicles and their growth and development seems to rely on an early burst of neovascularization in which vascular endothelial growth factor-A (VEGF-A) is the main and most powerful factor involved (Larcher et al, 1996(Larcher et al, , 1998Detmar, 2000a).…”

Section: Introductionmentioning

confidence: 99%

An inactivating CYLD mutation promotes skin tumor progression by conferring enhanced proliferative, survival and angiogenic properties to epidermal cancer cells

et al. 2010

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In this study, we demonstrate that the expression in tumorigenic epidermal cells of a catalytically inactive form of CYLD (CYLD C/S ) that mimics the identified mutations of cyld in human tumors and competes with the endogenous CYLD results in enhanced cell proliferation and inhibition of apoptosis; it also stimulates cell migration and induces the expression of angiogenic factors, including vascular endothelial growth factor-A. Altogether, these characteristics indicate an increased oncogenicity of the tumorigenic epidermal CYLD C/S mutant cells in vitro. Moreover, we show the increase in malignancy of epidermal squamous cell carcinomas that express the CYLD C/S transgene in an in vivo xenograft model. Tumors carrying the mutated CYLD C/S exhibit a fast growth, are poorly differentiated and present a robust angiogenesis. CYLD C/S tumors are also characterized by their elevated proliferation rate and decreased apoptosis. In contrast with previous studies showing the development of benign tumors by mutations in the CYLD gene, here we provide evidence that the occurrence of mutations in the CYLD gene in tumorigenic epidermal cells (carrying previous mutations) increases the aggressiveness of carcinomas, mainly through enhancement of the expression of angiogenic factors, having therefore a key role in epidermal cancer malignancy.

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“…New blood vessels formation from existing vasculature is termed as angiogenesis, a crucial pathway for tissue repair, growth and embryogenesis (Cherrington et al, 2000, Ferrara, 2002, Harmange et al, 2008 and associated with different types of pathological processes which include metastasis (Liotta et al, 1991), tumor growth (Folkman, 1972), psoriasis (Detmar, 2000), ocular neovascularization (Aiello et al, 1994), rheumatoid . arthritis (Walsh and Haywood, 2001), inflammation (Fava, 1994). Vascular endothelial growth factor (VEGFa) and its receptor tyrosine kinases VEGFR-2 or kinase insert domain receptor (KDR) and VEGFR-1 were reported as key regulators for angiogenesis (Terman et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

In silico ADME/T and 3D QSAR analysis of KDR inhibitors

Hosen¹,

Dash²,

Khatun³

et al. 2017

J App Pharm Sci

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Tyrosine kinases (KDR) have been considered as a potential targets for the design of new anticancer agents. Recently, a series of N-4-chlorophenylnaphthamides has been reported with KDR inhibitory activity. In order to demonstrate the pharmacokinetics and the relationship between the structures and their inhibition of KDR, 3D-QSAR and in silico ADME/T analysis were performed on a dataset of 13 compounds. Quantum chemical parameters such as LUMO energy, HOMO energy, ionization energy (I), electron affinity (A), chemical potential (μ), hardness (η) and electrophilicity (χ) of the compounds are calculated by using semi-empirical SCF-MO method at PM3 level of theory and various SlogP descriptors from MOE software. In silico ADME/T analysis was performed by using different software's Discovery Studio 2.5, TOPKAT and QikProp 4.3. From in silico ADME and Toxicity studies, it was revealed that selected derivatives have good oral absorption rate and metabolism with no BBB penetration. QSTR (Quantitative Structure Toxicity Relationship) studies by using TOPAK in various computational animal models, showed high LD50 values and the compounds are found to be noncarcenogenic. Moreover, three different QSAR models were generated by Partial Least Squares (PLS) Regression method having correlation coefficient (Q 2 ) of 0.86382, 0.84372, and 0.82629, respectively. These models conclude a significant relationship of KDR inhibition with dipole moment (D), LUMO energy (ELUMO), hardness (η) and electrophilicity (χ), and hydrophobicity of compounds, regarding N-4-chlorophenylnaphthamides.

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The role of VEGF and thrombospondins in skin angiogenesis

Cited by 156 publications

References 27 publications

Vasculostatin, a proteolytic fragment of Brain Angiogenesis Inhibitor 1, is an antiangiogenic and antitumorigenic factor

Vasculostatin, a proteolytic fragment of Brain Angiogenesis Inhibitor 1, is an antiangiogenic and antitumorigenic factor

An inactivating CYLD mutation promotes skin tumor progression by conferring enhanced proliferative, survival and angiogenic properties to epidermal cancer cells

In silico ADME/T and 3D QSAR analysis of KDR inhibitors

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