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EDITORIAL

Marco Presta¹, Domenico Ribatti²
European Cytokine Network, Vol.20, No.4, pp. 157-157, 2009, DOI:10.1684/ecn.2009.0171
Abstract This article has no abstract. More >

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Napoleone Ferrara
European Cytokine Network, Vol.20, No.4, pp. 158-163, 2009, DOI:10.1684/ecn.2009.0170
Abstract Angiogenesis is required for a variety of normal and pathological, proliferative processes. Numer-ous regulators of angiogenesis have been identified and characterized over the last decades. Among these, vas-cular endothelial growth factor (VEGF)-A appears especially important in normal development and in disease processes. Several VEGF inhibitors have been approved by the FDA for the treatment of tumors or the neovas-cular form of age-related macular degeneration. This article examines the molecular and biological characteris-tics of VEGF and also discusses preclinical and clinical studies with VEGF inhibitors and the lessons learned from these studies. More >

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Marina Ziche, Lucia Morbidelli
European Cytokine Network, Vol.20, No.4, pp. 164-170, 2009, DOI:10.1684/ecn.2009.0169
Abstract As tumors grow, their original vasculature can be insufficient to supply the growing tissue mass, and consequently local hypoxia develops. Thus neovascularisation is a key feature determining growth and metastasis of malignant tumors. This is, at least in part, mediated by humoral factors known to stimulate angio-genesis, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). Among the multiple angiogenic modulators released by tumor and stromal cells, a key role is played by nitric oxide (NO). Beside its capacity to regulate permeability and blood flow, NO has been reported to exert angiogenic More >

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Nikos E. Tsopanoglou, Michael E. Maragoudakis
European Cytokine Network, Vol.20, No.4, pp. 171-179, 2009, DOI:10.1684/ecn.2009.0166
Abstract A plethora of endogenous modulators of angiogenesis have been identified and their roles in the molecular and cellular events that mediate and regulate angiogenesis have been proposed. In this review, we summarize the recent findings on the role of thrombin/thrombosis on angiogenesis and other related pathophys-iological processes. The mechanisms by which thrombin itself and its receptor PAR1 orchestrate many cellular events through interaction with a variety of other factors and cell types are discussed. These new data point to the complexity of the regulatory processes involved in the angiogenic cascade, which may be tissue specific, More >

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Evangelia Papadimitriou, Constantinos Mikelis, Evgenia Lampropoulou, Marina Koutsioumpa, Katerina Theochari, Sotiria Tsirmoula, Christina Theodoropoulou, Margarita Lamprou, Evanthia Sfaelou, Dionyssios Vourtsis, Panagiotis Boudouris
European Cytokine Network, Vol.20, No.4, pp. 180-190, 2009, DOI:10.1684/ecn.2009.0172
Abstract Pleiotrophin (PTN) is a heparin-binding growth factor with diverse biological activities, the moststudied of these being those related to the nervous system, tumor growth and angiogenesis. Although interest inthe involvement of PTN in tumor growth is increasing, many questions remain unanswered, particularly con-cerning the receptors and the signaling pathways involved. In this review, we briefly introduce PTN, and sum-marize data on its involvement in tumor growth and angiogenesis, and on what is known to date concerningthe receptors and pathways involved. More >

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Federico Bussolino, Francesca Caccavari, Donatella Valdembri, Guido Serini
European Cytokine Network, Vol.20, No.4, pp. 191-196, 2009, DOI:10.1684/ecn.2009.0168
Abstract Acquisition of new genes encoding for extracellular matrix (ECM) proteins and their cognate integrin adhesive receptors, as well as secreted pro- and anti-angiogenic factors, proved to be essential for the development of functional vascular networks in the vertebrate embryo. There is now clear evidence that post-natal, pathological tissue neo-vascularization is crucial for cancer growth and therapy as well. Integrins are major ECM receptors that can exist in different functional states with respect to their affinity for ECM pro-teins. Regulation of integrin activation is crucial for their biological functions. In the embryo, the development of a More >

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Enrico Crivellato¹, Beatrice Nico², Domenico Ribatti²
European Cytokine Network, Vol.20, No.4, pp. 197-206, 2009, DOI:10.1684/ecn.2009.0167
Abstract Mast cells (MCs) are tissue leukocytes that are distributed throughout the major organs of the body. They are an important local source of preformed and newly synthesized angiogenic molecules. MCs have been linked both to inflammatory and tumor angiogenesis. Indeed, numerous solid tumors and hematological malignancies present MC-rich infiltrates, which are believed to contribute to the formation of a new vascular supply. In addition, angiogenesis and MC density have been shown to increase simultaneously with the pathological progression in many of such tumors. This review will focus on the angiogenic potential of MCs in human More >

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Robert E. Verloop¹, Pieter Koolwijk¹, Anton Jan van Zonneveld², Victor W. M. van Hinsbergh¹
European Cytokine Network, Vol.20, No.4, pp. 207-219, 2009, DOI:10.1684/ecn.2009.0174
Abstract Since the initial discovery of endothelial progenitor cells (EPC), and their promise in increasing angiogen-esis and vasculogenesis, a myriad of papers have highlighted their potential application in experimental and clinical neo-vascularization and in tissue engineering. However, promising reports are contrasted by other studies that could not find a role for EPC in neovascularization. Presently, two types of endothelial progenitor cell populations are recognized. The first population provides early-outgrowth CD34⁺ /VEGFR-2⁺ cells, or colony-forming unit endothelial cells (CFU-EC), which represent myeloid cells with some endothelial properties, but no ability to form endothelial colonies. They can stimulate neovascularization… More >

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Yasufumi Sato
European Cytokine Network, Vol.20, No.4, pp. 220-224, 2009, DOI:10.1684/ecn.2009.0173
Abstract Angiogenesis is regulated by the local balance between angiogenesis stimulators and inhibitors. A number of endogenous angiogenesis inhibitors have been found in the body. The origin of these inhibitors is mostly extrinsic to the vasculature. Recently however, endothelial cells themselves have been found to produce angiogenesis inhibitors including delta-like 4 and vasohibin 1. These intrinsic factors are thought to regulate angiogenesis by an autoregulatory or negative-feedback mechanism. This review focuses on such negative regu-lators of angiogenesis produced by endothelial cells. More >

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Patrizia Alessi¹, Daria Leali¹, Maura Camozzi¹, AnnaRita Cantelmo², Adriana Albini², Marco Presta¹
European Cytokine Network, Vol.20, No.4, pp. 225-234, 2009, DOI:10.1684/ecn.2009.0175
Abstract Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, plays a pivotal role in tumor growth, progression and metastasis. Over the last 30 years, numerous pro- and antiangiogenic molecules, their ligands, and intracellular signaling pathways have been identified, and signifi-cant efforts have been undertaken to develop antiangiogenic strategies for cancer therapy. Agents that selec-tively target vascular endothelial growth factor (VEGF) and its receptors have shown promising activity in clin-ical trials and have been approved for use in selected cancer indications. However, patients may ultimately develop resistance to these drugs. One… More >

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