Biological and molecular properties of a new αvβ3/αvβ5 integrin antagonist

Belvisi, Laura; Riccioni, Teresa; Marcellini, Marcella; Vesci, Loredana; Chiarucci, Ilaria; Efrati, Daniela; Potenza, Donatella; Scolastico, Carlo; Manzoni, Leonardo; Lombardo, Katia; Stasi, Maria Antonietta; Orlandi, Augusto; Ciucci, Alessandro; Nico, Beatrice; Ribatti, Doménico; Giannini, Giuseppe; Presta, Marco; Carminati, Paolo; Pisano, Claudio

doi:10.1158/1535-7163.mct-05-0120

Cited by 71 publications

(48 citation statements)

References 55 publications

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“…Similar to trans-resveratrol, RGD-derived a v h 3 integrin antagonists affect endothelial cell adhesion, proliferation, invasion, and morphogenesis when added to endothelial cell cultures in a micromolar range of concentrations (19,21). Thus, our results support the hypothesis that interaction of trans-resveratrol with the h 3 integrin chain may lead to inhibition of a v h 3 integrin activity.…”

Section: Discussionmentioning

confidence: 99%

αvβ3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers

Belleri

Ribatti

Savio

et al. 2008

Molecular Cancer Therapeutics

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Angiogenesis is target for antineoplastic and chemopreventive therapies. The natural phytoalexin resveratrol is found in grapes and red wine as cis and trans stereoisomers. trans-Resveratrol shows antiangiogenic activity, but its mechanism of action is not fully elucidated. Recently, trans-resveratrol has been shown to interact with the B 3 integrin subunit, raising the possibility that inhibition of endothelial A v B 3 integrin function may concur to its angiosuppressive activity. To get novel insights about the antiangiogenic activity of resveratrol, we compared cis-and trans-resveratrol stereoisomers for their effect on the angiogenesis process and endothelial A v B 3 integrin function. trans-Resveratrol inhibits endothelial cell proliferation and the repair of mechanically wounded endothelial cell monolayers. Also, it prevents endothelial cell sprouting in fibrin gel, collagen gel invasion, and morphogenesis on Matrigel. In vivo, trans-resveratrol inhibits vascularization of the chick embryo area vasculosa and murine melanoma B16 tumor growth and neovascularization. In all the assays, cis-resveratrol exerts a limited, if any, effect. In keeping with these observations, transresveratrol, but not cis-resveratrol, inhibits A v B 3 integrindependent endothelial cell adhesion and the recruitment of enhanced green fluorescent protein-tagged B 3 integrin in focal adhesion contacts. In conclusion, stereoisomery affects the antiangiogenic activity of resveratrol, the trans isomer being significantly more potent than the cis isoform. The different antiangiogenic potential of resveratrol stereoisomers is related, at least in part, to their different capacity to affect A v B 3 integrin function. This may have profound implications for the design of synthetic antiangiogenic/angiopreventive phytoalexin derivatives.

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Section: Discussionmentioning

confidence: 99%

αvβ3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers

Belleri

Ribatti

Savio

et al. 2008

Molecular Cancer Therapeutics

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“…Therefore, they can be used as biomarkers for diagnosis and prognosis, and as novel molecular therapeutic targets [29,30] .…”

Section: Discussionmentioning

confidence: 99%

Correlation of integrin β3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma

Li¹,

Ye²,

Zhao³

et al. 2008

WJG

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peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type (P < 0.01), stage T1-T2 (P < 0.01), non-vessel invasion (P < 0.01), without lymphatic metastasis (P < 0.01), without hepatic and peritoneal metastasis (P < 0.01), respectively. It was found that the positive expression rate of integrin β3 mRNA was positively related to that of VEGF protein (P < 0.01) and MVD (P < 0.05), meanwhile the positive expression rate of VEGF protein was positively related to MVD (P < 0.05). The mean survival period in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥ 54.9/mm 2 was significantly shorter than that in patients with negative expression of integrin β3 mRNA (P < 0.05) and VEGF (P < 0.01), and MVD < 54.9/mm 2 (P < 0.01). Five-year survival rate in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥ 54.9/mm 2 was significantly lower than those with negative expression of integrin β3 mRNA (P < 0.05), VEGF (P < 0.05), and MVD < 54.9/mm 2 (P < 0.01). CONCLUSION:Integrin β3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets. INTRODUCTIONGastric cancer is the leading cause of death in China. Abstract AIM: To investigate integrin β3 mRNA and vascular endothelial growth factor (VEGF) protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis. METHODS: In situ hybridization (ISH) of integrin β3mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer. RESULTS:The positive rate of integrin β3 mRNA in nontumor gastric mucosa (20%) was significantly lower than that of the gastric cancer tissue (52.5%, χ 2 = 10.20,

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“…Anti-angiogenic strategies have been pursued for cancer treatment and prevention of cancer recurrence and metastasis. Treatment with antagonists of either αV integrins or VEGF has been shown to exert significant anti-angiogenic activity and inhibit tumor formation [29,30]. Targeting of integrin αVβ3 receptor with specific antibodies has been demonstrated to synergize with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts [31], suggesting that combination treatment of anti-αV integrins or VEGF antibodies with either aggressive chemotherapy or radiotherapy will be a putative therapeutic strategy for osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of αV Integrin and VEGF in Osteosarcoma after Chemotherapy

Huang

Zhang²,

Zhuang³

et al. 2008

Onkologie

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Background: αV integrins and vascular endothelial growth factor (VEGF) have been shown to play an important role in osteosarcoma metastasis. However, their expression in osteosarcoma after chemotherapy remains unknown. Patients and Methods: Here, using immunohistochemistry, we analyzed the levels of αV integrins and VEGF in paraffin sections of 20 patients with untreated osteosarcoma, and 31 patients with adriamycin/cisplatin/ifosfamide-treated osteosarcoma. Results: Expression of αV integrins and VEGF was much higher in osteosarcoma compared with normal bone tissues (p < 0.001) and was reduced dramatically after adriamycin/cisplatin/ifosfamide treatment (p < 0.01). Their expression in osteosarcoma after chemotherapy positively correlated with each other (r = 0.418; p = 0.019, Spearman test). The rank sum test indicated that both positively correlated with osteosarcoma relapse (p < 0.01 and p < 0.05, respectively), Enneking stages (p < 0.05), and invasion of osteosarcoma (p < 0.05), but not with gender, age, tumor necrosis, tumor subtype, or location. VEGF expression was also associated with metastasis incidence (p < 0.05). Multinomial forward conditional logistic regression analysis showed that αV integrins might be an independent risk factor of osteosarcoma relapse (odds ratio = 3.96, p = 0.047, 95% confidence interval = (2.12–12.47)). Conclusion: Expression of αV integrins and expression of VEGF may be helpful indicators of osteosarcoma diagnosis and predictors of prognosis after chemotherapy, serving as putative targets for osteosarcoma treatment.

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Biological and molecular properties of a new αvβ3/αvβ5 integrin antagonist

Cited by 71 publications

References 55 publications

αvβ3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers

αvβ3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers

Correlation of integrin β3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma

Prognostic Significance of αV Integrin and VEGF in Osteosarcoma after Chemotherapy

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Biological and molecular properties of a new αvβ3/αvβ5 integrin antagonist

Cited by 71 publications

References 55 publications

αvβ3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers

αvβ3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers

Correlation of integrin β3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma

Prognostic Significance of &alpha;V Integrin and VEGF in Osteosarcoma after Chemotherapy

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Prognostic Significance of αV Integrin and VEGF in Osteosarcoma after Chemotherapy