Tumor Angiogenesis

Total Page:16

File Type:pdf, Size:1020Kb

Tumor Angiogenesis Journal of Oncology Tumor Angiogenesis Guest Editors: Arkadiusz Dudek, Kalpna Gupta, Sundaram Ramakrishnan, and Debabrata Mukhopadhyay Tumor Angiogenesis Journal of Oncology Tumor Angiogenesis Guest Editors: Arkadiusz Dudek, Kalpna Gupta, Sundaram Ramakrishnan, and Debabrata Mukhopadhyay Copyright © 2010 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in volume 2010 of “Journal of Oncology.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Journal of Oncology Editorial Board Thomas E. Adrian, UAE Andreas H. Jacobs, Germany Dirk Rades, Germany Massimo Aglietta, Italy Ismail Jatoi, USA Zvi Ram, Israel Bruce Baguley, New Zealand G. Kaspers, The Netherlands Dirk Reinhardt, Germany David Ball, Australia Michael J. Kerin, Ireland Paul G. Richardson, USA A. J. M. Balm, The Netherlands Turker¨ Kilic¸, Turkey Michel Rigaud, France Frederic G. Barr, USA Timothy J. Kinsella, USA Jorg¨ Ritter, Germany Søren M. Bentzen, USA Jorg¨ Kleeff,Germany Mack Roach, USA Rolf Bjerkvig, Norway George O. Klein, Sweden BerndF.M.Romeike,Germany Peter McLaren Black, USA Mark J. Krasna, USA Volker Rudat, Germany Susana M. Campos, USA Masatoshi Kudo, Japan Thomas J. Rutherford, USA Michael A. Carducci, USA Robert Langley, USA Aysegula A. Sahin, USA Stefano Cascinu, Italy Charles F. Levenback, USA Giovanni Scambia, Italy Soonmee Cha, USA Allan Lipton, USA P. Magnus Schneider, Switzerland Susan Chang, USA Jay S. Loeffler, USA Peter E. Schwartz, USA Thomas R. Chauncey, USA Dario Marchetti, USA Jalid Sehouli, Germany Dennis S. Chi, USA Maurie M. Markman, USA Edgar Selzer, Austria Edward A. Copelan, USA Shahla Masood, USA Francis Seow-Choen, Singapore Richard Crevenna, Austria Keisuke Masuyama, Japan Dong M. Shin, USA Massimo Cristofanilli, USA Ian E. McCutcheon, USA Jean F. Simpson, USA Christos Dervenis, Greece Minesh Mehta, USA Keshav K. Singh, USA Andreas Dietz, Germany Sofia D. Merajver, USA Judith A. Smith, USA Frederick E. Domann, USA Bradley J. Monk, USA Lawrence J. Solin, USA Avraham Eisbruch, USA Yoshihiro Moriya, Japan Luis Souhami, Canada Joann G. Elmore, USA Satoru Motoyama, Japan Alphonse G. Taghian, USA Thomas J. Fahey, USA JamesL.Mulshine,USA Hiromitsu Takeyama, Japan Dominic Fan, USA Arya Nabavi, Germany Nelson Teng, USA Phillip G. Febbo, USA Patrick Neven, Belgium C. H. J. Terhaard, The Netherlands Douglas L. Fraker, USA Felix Niggli, Switzerland Douglas S. Tyler, USA Henry S. Friedman, USA Patrizia Olmi, Italy Raul A. Urrutia, USA Hani Gabra, UK Jan I. Olofsson, Norway Vincenzo Valentini, Italy Cicek Gercel-Taylor, USA Jens Overgaard, Denmark Daniel Vallbohmer,¨ Germany William J. Gradishar, USA Richard T. Penson, USA M. W. M. van den Brekel, The Netherlands Robert M. Hermann, Germany Joseph M. Piepmeier, USA G. A. M. S. Van Dongen, The Netherlands Mario Hermsen, Spain Rob Pieters, The Netherlands John R. van Nagell, USA Fred H. Hochberg, USA M. Steven Piver, USA Bruno Vincenzi, Italy William J. Hoskins, USA Alfredo Quinones-Hinojosa, USA Dennis D. Weisenburger, USA Toshiyuki Ishiwata, Japan JanetS.Rader,USA Jochen A. Werner, Germany Contents Tumor Angiogenesis, Arkadiusz Dudek, Kalpna Gupta, Sundaram Ramakrishnan, and Debabrata Mukhopadhyay Volume 2010, Article ID 761671, 2 pages Tumor Angiogenesis: Insights and Innovations, Fernando Nussenbaum and Ira M. Herman Volume 2010, Article ID 132641, 24 pages Extracellular Matrix Proteins and Tumor Angiogenesis,N.E.Campbell,L.Kellenberger,J.Greenaway, R. A. Moorehead, N. M. Linnerth-Petrik, and J. Petrik Volume 2010, Article ID 586905, 13 pages Eph Receptors and Ephrin Ligands: Important Players in Angiogenesis and Tumor Angiogenesis, Birgit Mosch, Bettina Reissenweber, Christin Neuber, and Jens Pietzsch Volume 2010, Article ID 135285, 12 pages Myeloid Cells in the Tumor Microenvironment: Modulation of Tumor Angiogenesis and Tumor Inflammation, Michael C. Schmid and Judith A. Varner Volume 2010, Article ID 201026, 10 pages Sympathetic Neurotransmitters and Tumor Angiogenesis—Link between Stress and Cancer Progression, Jason Tilan and Joanna Kitlinska Volume 2010, Article ID 539706, 6 pages IL-17B Can Impact on Endothelial Cellular Traits Linked to Tumour Angiogenesis, Andrew J. Sanders, Xiaoxia Guo, Malcolm D. Mason, and Wen G. Jiang Volume 2010, Article ID 817375, 5 pages An Active Form of Sphingosine Kinase-1 Is Released in the Extracellular Medium as Component of Membrane Vesicles Shed by Two Human Tumor Cell Lines, Salvatrice Rigogliuso, Chiara Donati, Donata Cassara,` Simona Taverna, Monica Salamone, Paola Bruni, and Maria Letizia Vittorelli Volume 2010, Article ID 509329, 10 pages Hsp90 as a Gatekeeper of Tumor Angiogenesis: Clinical Promise and Potential Pitfalls,J.E.Bohonowych, U. Gopal, and J. S. Isaacs Volume 2010, Article ID 412985, 17 pages The Role of Ets Factors in Tumor Angiogenesis, Peter Oettgen Volume 2010, Article ID 767384, 6 pages Molecular Mechanisms of Resistance to Tumour Anti-Angiogenic Strategies,RenaudGrepin´ and Gilles Pages` Volume 2010, Article ID 835680, 8 pages Molecular and Clinical Aspects of Targeting the VEGF Pathway in Tumors, Grzegorz Korpanty, Laura A. Sullivan, Elizabeth Smyth, Desmond N. Carney, and Rolf A. Brekken Volume 2010, Article ID 652320, 12 pages TGF-β Superfamily Receptors—Targets for Antiangiogenic Therapy?, Jasmin Otten, Carsten Bokemeyer, and Walter Fiedler Volume 2010, Article ID 317068, 10 pages Architectural Heterogeneity in Tumors Caused by Differentiation Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound,YoucefM.Rustum, Karoly´ Toth,´ Mukund Seshadri, Arindam Sen, Farukh A. Durrani, Emily Stott, Carl D. Morrison, Shousong Cao, and Arup Bhattacharya Volume 2010, Article ID 396286, 13 pages Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy, Han-Chung Wu and De-Kuan Chang Volume 2010, Article ID 723798, 8 pages Angiogenesis Inhibition in Prostate Cancer: Current Uses and Future Promises, Jeanny B. Aragon-Ching, Ravi A. Madan, and William L. Dahut Volume 2010, Article ID 361836, 7 pages CXCL7-Mediated Stimulation of Lymphangiogenic Factors VEGF-C, VEGF-D in Human Breast Cancer Cells, Minghuan Yu, Richard Berk, and Mary Ann Kosir Volume 2010, Article ID 939407, 10 pages Immunomodulatory Agents with Antivascular Activity in the Treatment of Non-Small Cell Lung Cancer: Focus on TLR9 Agonists, IMiDs and NGR-TNF, Angelo Corti, Monica Giovannini, Carmen Belli, and Eugenio Villa Volume 2010, Article ID 732680, 8 pages Angiogenesis: From Chronic Liver Inflammation to Hepatocellular Carcinoma, Paloma Sanz-Cameno, Mar´ıa Trapero-Marugan,´ Mar´ıa Chaparro, Evan Anthony Jones, and Ricardo Moreno-Otero Volume 2010, Article ID 272170, 7 pages Angiogenesis and Lymphangiogenesis of Gastric Cancer, Yasuhiko Kitadai Volume 2010, Article ID 468725, 8 pages Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides, Christina Coleman, Danielle Levine, Raj Kishore, Gangjian Qin, Tina Thorne, Erin Lambers, Sharath P. Sasi, Mina Yaar, Barbara A. Gilchrest, and David A. Goukassian Volume 2010, Article ID 928628, 14 pages Molecular Therapeutic Targets for Glioma Angiogenesis, Shingo Takano, Toshiharu Yamashita, and Osamu Ohneda Volume 2010, Article ID 351908, 11 pages Progress on Antiangiogenic Therapy for Patients with Malignant Glioma,ManmeetS.Ahluwaliaand Candece L. Gladson Volume 2010, Article ID 689018, 14 pages Antiangiogenic Therapy and Mechanisms of Tumor Resistance in Malignant Glioma, Ruman Rahman, Stuart Smith, Cheryl Rahman, and Richard Grundy Volume 2010, Article ID 251231, 16 pages Ganglioside GM3 Is Antiangiogenic in Malignant Brain Cancer, Thomas N. Seyfried and Purna Mukherjee Volume 2010, Article ID 961243, 8 pages Role of Angiopoietin-2 in Regulating Growth and Vascularity of Astrocytomas, Gelareh Zadeh, Keyvan Koushan, Qian Baoping, Patrick Shannon, and Abhijit Guha Volume 2010, Article ID 659231, 7 pages Vascular Endothelial Growth Factor-Related Pathways in Hemato-Lymphoid Malignancies, Michael Medinger, Natalie Fischer, and Alexandar Tzankov Volume 2010, Article ID 729725, 13 pages Hindawi Publishing Corporation Journal of Oncology Volume 2010, Article ID 761671, 2 pages doi:10.1155/2010/761671 Editorial Tumor Angiogenesis Arkadiusz Dudek,1 Kalpna Gupta,1 Sundaram Ramakrishnan,2 and Debabrata Mukhopadhyay3 1 Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA 2 Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA 3 Department of Biochemistry and Molecular Biology, Tumor Angiogenesis, Vascular Biology and Nanotechnology Laboratory, Mayo Clinic Foundation, Rochester, MN, USA Correspondence should be addressed to Arkadiusz Dudek, [email protected] Received 30 August 2010; Accepted 30 August 2010 Copyright © 2010 Arkadiusz Dudek et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In a seminal New England Journal of Medicine article, pub- and result in resumption of tumor dormancy. The fourth lished 40 years ago, Folkman proposed the concept that assumption was that antiangiogenic cancer therapy could angiogenesis could be a target for cancer therapy [1]. This be
Recommended publications
  • Molecular Targeted and Immune Checkpoint Therapy for Advanced
    Liu et al. Journal of Experimental & Clinical Cancer Research (2019) 38:447 https://doi.org/10.1186/s13046-019-1412-8 REVIEW Open Access Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma Ziyu Liu1†, Yan Lin2†, Jinyan Zhang2, Yumei Zhang2, Yongqiang Li2, Zhihui Liu2, Qian Li2, Ming Luo2, Rong Liang2* and Jiazhou Ye3* Abstract Molecular targeted therapy for advanced hepatocellular carcinoma (HCC) has changed markedly. Although sorafenib was used in clinical practice as the first molecular targeted agent in 2007, the SHARPE and Asian-Pacific trials demonstrated that sorafenib only improved overall survival (OS) by approximately 3 months in patients with advanced HCC compared with placebo. Molecular targeted agents were developed during the 10-year period from 2007 to 2016, but every test of these agents from phase II or phase III clinical trial failed due to a low response rate and high toxicity. In the 2 years after, 2017 through 2018, four successful novel drugs emerged from clinical trials for clinical use. As recommended by updated Barcelona Clinical Liver cancer (BCLC) treatment algorithms, lenvatinib is now feasible as an alternative to sorafenib as a first-line treatment for advanced HCC. Regorafenib, cabozantinib, and ramucirumab are appropriate supplements for sorafenib as second-line treatment for patients with advanced HCC who are resistant, show progression or do not tolerate sorafenib. In addition, with promising outcomes in phase II trials, immune PD-1/PD-L1 checkpoint inhibitors nivolumab and pembrolizumab have been applied for HCC treatment. Despite phase III trials for nivolumab and pembrolizumab, the primary endpoints of improved OS were not statistically significant, immune PD-1/PD-L1 checkpoint therapy remains to be further investigated.
    [Show full text]
  • Proteolytic Cleavages in the Extracellular Domain of Receptor Tyrosine Kinases by Membrane-Associated Serine Proteases
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 34), pp: 56490-56505 Research Paper Proteolytic cleavages in the extracellular domain of receptor tyrosine kinases by membrane-associated serine proteases Li-Mei Chen1 and Karl X. Chai1 1Burnett School of Biomedical Sciences, Division of Cancer Research, University of Central Florida College of Medicine, Orlando, FL 32816-2364, USA Correspondence to: Karl X. Chai, email: [email protected] Keywords: receptor tyrosine kinase, matriptase, prostasin, Herceptin, breast cancer Received: August 05, 2016 Accepted: March 21, 2017 Published: April 10, 2017 Copyright: Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA). Western blot analysis was performed to detect the carboxyl-terminal fragments (CTFs) of the RTKs. Matriptase and hepsin were found to cleave the ECD of all RTKs tested, while TMPRSS6/matriptase-2 cleaves the ECD of Her4, INSR, and PDGFR α and β.
    [Show full text]
  • Role of EFNB2/EPHB4 Signaling in Spiral Artery Development During Pregnancy: an Appraisal
    ESSAY Molecular Reproduction & Development 83:12–18 (2016) Role of EFNB2/EPHB4 Signaling in Spiral Artery Development During Pregnancy: An Appraisal HONGMEI DONG,* CHAORAN YU, JIAO MU, JI ZHANG, AND WEI LIN Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China SUMMARY EFNB2 and EPHB4, which belong to a large tyrosine kinase receptor superfamily, are molecular markers of arterial and venous blood vessels, respectively. EFNB2/ EPHB4 signaling plays an important role in physiological and pathological angiogen- esis, and its role in tumor vessel development has been extensively studied. [W]e hypothesize that changing Pregnancy and tumors share similar features, including continuous cell proliferation the distinct spatiotemporal and increased demand for a blood supply. Our previous studies showed that Efnb2 expression of EFNB2/ Ephb4 and were expressed dynamically in the spiral arteries, uterine natural killer EPHB4...contributes to spiral À cells, and trophoblasts during mouse gestation Days 6.5 12.5. Moreover, uterine artery remodeling. natural killer cells and trophoblasts are required for the modification of spiral arteries. Oxygen tension within the pregnant uterus, which contributes to the vascular development, also affects EFNB2 and EPHB4 expression. Considering the role of ÃCorresponding author: EFNB2/EPHB4 signaling in embryonic and tumor vascular development, and its Department of Forensic Medicine Tongji Medical College of dynamic expression in the decidua and placenta, we hypothesize that EFNB2 and Huazhong University of EPHB4 are involved in the regulation of spiral artery remodeling. Investigating this Science and Technology hypothesis will help clarify the mechanisms of pathological pregnancy that may 13 Hangkong Road Wuhan, Hubei 430030, P.
    [Show full text]
  • Angiopoietin 1 and Vascular Endothelial Growth Factor Modulate Human Glomerular Endothelial Cell Barrier Properties
    J Am Soc Nephrol 15: 566–574, 2004 Angiopoietin 1 and Vascular Endothelial Growth Factor Modulate Human Glomerular Endothelial Cell Barrier Properties SIMON C. SATCHELL, KAREN L. ANDERSON, and PETER W. MATHIESON Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom Abstract. Normal glomerular filtration depends on the com- porous supports were investigated by measurement of transen- bined properties of the three layers of glomerular capillary dothelial electrical resistance (TEER) and passage of labeled wall: glomerular endothelial cells (GEnC), basement mem- albumin. Responses to a cAMP analogue and thrombin were brane, and podocytes. Podocytes produce endothelial factors, examined before those to ang1 and VEGF. Results confirmed including angiopoietin 1 (ang1), and vascular endothelial the endothelial origin of GEnC and their expression of Tie2 growth factor (VEGF), whereas GEnC express their respective and VEGFR2. GEnC formed monolayers with a mean TEER receptors Tie2 and VEGFR2 in vivo. As ang1 acts to maintain of 30 to 40 ⍀/cm2. The cAMP analogue and thrombin in- the endothelium in other vascular beds, regulating some ac- creased and decreased TEER by 34.4 and 14.8 ⍀/cm2, respec- tions of VEGF, these observations suggest a mechanism tively, with corresponding effects on protein passage. Ang1 whereby podocytes may direct the unique properties of the increased TEER by 11.4 ⍀/cm2 and reduced protein passage glomerular endothelium. This interaction was investigated by by 45.2%, whereas VEGF reduced TEER by 12.5 ⍀/cm2 but studies on the barrier properties of human GEnC in vitro. had no effect on protein passage. Both ang1 and VEGF mod- GEnC were examined for expression of endothelium-specific ulate GEnC barrier properties, consistent with potential in vivo markers by immunofluorescence and Western blotting and for roles; ang1 stabilizing the endothelium and resisting angiogen- typical responses to TNF-␣ by a cell-based immunoassay.
    [Show full text]
  • Expression and Hypoxic Regulation of Angiopoietins in Human Astrocytomas 1
    Neuro-Oncology Expression and hypoxic regulation of angiopoietins in human astrocytomas 1 Hao Ding, Luba Roncari, Xiaoli Wu, Nelson Lau, Patrick Shannon, Andras Nagy, and Abhijit Guha 2 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G-1X5 (H.D., L.R., X.W., N.L., A.N., A.G.); and Division of Neurosurgery, Division of Neuropathology, Department of Pathology and Laboratory Medicine, The Toronto Hospital and University of Toronto, Ontario, Canada M5T-2S8 (P.S., A.G.) Vascular endothelial growth factor (VEGF) is a major studies. Ang2 expression in the highly proliferative tumor inducer of tumor angiogenesis and edema in human astro- vascular endothelium was also increased, as was phos- cytomas by its interaction with cognate endothelial-spe- phorylated Tie2/Tek. The expression prole of these cic receptors (VEGFR1/R2). Tie1 and Tie2/Tek are angiogenic factors and their endothelial cell receptors in more recently identied endothelial-specic receptors, human glioblastomas multiforme was similar to that in a with angiopoietins being ligands for the latter. These transgenic mouse model of glioblastoma multiforme. angiogenic factors and receptors are crucial for the matu- These data suggest that both VEGF and angiopoietins ration of the vascular system, but their role in tumor are involved in regulating tumor angiogenesis in human angiogenesis, particularly in astrocytomas, is unknown. astrocytomas. Neuro-Oncology 3, 1–10, 2001 (Posted to In this study, we demonstrate that the angiopoietin family Neuro-Oncology [serial online], Doc. 00-031, November member Ang1 is expressed by some of the astrocytoma 7, 2000. URL <neuro-oncology.mc.duke.edu>) cell lines.
    [Show full text]
  • Regulation of Angiogenesis Via Vascular Endothelial Growth Factor Receptors1
    [CANCER RESEARCH 60, 203–212, January 15, 2000] Review Regulation of Angiogenesis via Vascular Endothelial Growth Factor Receptors1 Tanja Veikkola, Marika Karkkainen, Lena Claesson-Welsh, and Kari Alitalo2 Molecular/Cancer Biology Laboratory, Haartman Institute, University of Helsinki, SF-00014 Helsinki, Finland [T. V., M. K., K. A.], and Department of Medical Biochemistry and Microbiology, Biomedical Center, S-75123 Uppsala, Sweden [L. C-W.] Introduction Endothelial cell signal transduction mechanisms involved in angio- with several different isoforms generated by alternative splicing, genesis have come into focus in cancer research when it was realized consisting of polypeptides of 121, 145, 165, 189, or 206 amino acid that solid tumors are dependent on neovascularization (1). Unlike residues (15, 24–26). VEGF binds both VEGFR-1 and VEGFR-2 and normal human endothelial cells, which are quiescent except in the is apparently capable of inducing heterodimers between the two reproductive organs of fertile women, endothelial cells in tumors (27–30). VEGF uses symmetrical binding sites at each pole of the express several target features associated with their angiogenic acti- dimer for receptor binding (31, 32). It has been shown that the second vation. On the other hand, unlike the tumor cells, endothelial cells are immunoglobulin homology domain of VEGFR-1 is critical for ligand readily accessible from the blood circulation, and they are not likely binding, but the first three immunoglobulin domains are required to to develop resistant variants to cytostatic therapy (see Ref. 2). Vas- reconstitute full affinity (31, 33–35). Of the other VEGF family cular targeting may involve either the destruction of existing vessels members, PlGF and VEGF-B bind only VEGFR-1, the Orf virus by exploitation of differences between normal and tumor vessels VEGFs bind only VEGFR-2, and VEGF-C and VEGF-D interact with (3–6) or inhibition of the tumor angiogenesis process per se (7–9).
    [Show full text]
  • Brain Hemorrhages
    Brain Hemorrhages The role of mural cells in hemorrhage of brain arteriovenous malformation --Manuscript Draft-- Manuscript Number: Article Type: Review Article Keywords: Brain arteriovenous malformation; intracranial hemorrhage; mural cells; PDGF- B/PDGFR-β; EphrinB2/EphB4; angiopoietin1/tie2 Corresponding Author: Hua Su, MD University of California San Francisco San Francisco, CA UNITED STATES First Author: Peipei Pan, PhD Order of Authors: Peipei Pan, PhD Sonali S Shaligram, PhD Leandro Barbosa Do Prado, PhD Liangliang He, MD Hua Su, MD Abstract: Brain arteriovenous malformation (bAVM) is the most common cause of intracranial hemorrhage (ICH), particularly in young patients. However, the exact cause of bAVM bleeding and rupture is not yet fully understood. In bAVMs, blood bypasses the entire capillary bed and directly flows from arteries to veins. The vessel walls in bAVMs have structural defects, which impair vascular integrity. Mural cells are essential structural and functional components of blood vessels and play critical rols in maintaining vascular integrity. Changes in mural cell number and coverage have been implicated in bAVMs. In this review, we discussed the roles of mural cells in bAVM pathogenesis. We focused on 1) the recent advances in human and animal studies of bAVMs; 2) the importance of mural cells in vascular integrity; 3) the regulatory signaling pathways that regulate mural cell function. More specifically, the platelet-derived growth factor B (PDGFB)/PDGF receptor β (PDGFRβ), EphrinB2/EphB4, and angiopoietin1/tie2 signaling pathways that regulate mural cell-recruitment during vascular remodeling were discussed in detail. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Cover Letter September 26, 2020 Dear Dr.
    [Show full text]
  • Angiopoietins, Vascular Endothelial Growth Factors and Secretory Phospholipase A2 in Ischemic and Non-Ischemic Heart Failure
    Journal of Clinical Medicine Article Angiopoietins, Vascular Endothelial Growth Factors and Secretory Phospholipase A2 in Ischemic and Non-Ischemic Heart Failure Gilda Varricchi 1,2,3,4,* , Stefania Loffredo 1,2,3,4,* , Leonardo Bencivenga 1,5 , Anne Lise Ferrara 1,2,3 , Giuseppina Gambino 1, Nicola Ferrara 1, Amato de Paulis 1,2,3, Gianni Marone 1,2,3,4 and Giuseppe Rengo 1,6 1 Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy; [email protected] (L.B.); [email protected] (A.L.F.); [email protected] (G.G.); [email protected] (N.F.); [email protected] (A.d.P.); [email protected] (G.M.); [email protected] (G.R.) 2 Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80100 Naples, Italy 3 World Allergy Organization (WAO), Center of Excellence, 80100 Naples, Italy 4 Institute of Experimental Endocrinology and Oncology “G. Salvatore” (IEOS), National Research Council (CNR), 80100 Naples, Italy 5 Department of Advanced Biomedical Sciences, University of Naples Federico II, 80100 Naples, Italy 6 Istituti Clinici Scientifici Maugeri SpA Società Benefit, Via Bagni Vecchi, 1, 82037 Telese BN, Italy * Correspondence: [email protected] (G.V.); stefanialoff[email protected] (S.L.) Received: 1 June 2020; Accepted: 17 June 2020; Published: 19 June 2020 Abstract: Heart failure (HF) is a growing public health burden, with high prevalence and mortality rates. In contrast to ischemic heart failure (IHF), the diagnosis of non-ischemic heart failure (NIHF) is established in the absence of coronary artery disease. Angiopoietins (ANGPTs), vascular endothelial growth factors (VEGFs) and secretory phospholipases A2 (sPLA2s) are proinflammatory mediators and key regulators of endothelial cells.
    [Show full text]
  • Regulation of Tie-2 by Angiopoietin-1 and Angiopoietin-2 in Endothelial Cells
    REGULATION OF TIE-2 BY ANGIOPOIETIN-1 AND ANGIOPOIETIN-2 IN ENDOTHELIAL CELLS By Elena Bogdanovic A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy, Department of Medical Biophysics, in the University of Toronto © Copyright 2009 by Elena Bogdanovic Elena Bogdanovic Regulation of Tie-2 by Angiopoietin-1 and Angiopoietin-2 in Endothelial Cells (2009) Doctor of Philosophy Department of Medical Biophysics, University of Toronto Abstract The tyrosine kinase receptor Tie-2 is expressed on the surface of endothelial cells and is necessary for angiogenesis and vascular stability. To date, the best characterized ligands for Tie- 2 are Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2). Ang-1 has been identified as the main activating ligand for Tie-2 while the role of Ang-2 has been controversial since its discovery; some studies reported Ang-2 as a Tie-2 antagonist while others described Ang-2 as a Tie-2 agonist. The purpose of this thesis was to understand: (1) how the receptor Tie-2 is regulated by Ang-1 and Ang-2 in endothelial cells, (2) to compare the effects of Ang-1 and Ang-2, and (3) to determine the arrangement and distribution of Tie-2 in endothelial cells. The research presented in this thesis indicates that Tie-2 is arranged in variably sized clusters on the endothelial cell surface. Clusters of Tie-2 were expressed on all surfaces of cells: on the apical plasma membrane, on the tips of microvilli, and on the basolateral plasma membrane. When endothelial cells were stimulated with Ang-1, Tie-2 was rapidly internalized and degraded.
    [Show full text]
  • Tie2 and Eph Receptor Tyrosine Kinase Activation and Signaling
    Downloaded from http://cshperspectives.cshlp.org/ on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Tie2 and Eph Receptor Tyrosine Kinase Activation and Signaling William A. Barton1, Annamarie C. Dalton1, Tom C.M. Seegar1, Juha P. Himanen2, and Dimitar B. Nikolov2 1Department of Biochemistry and Molecular Biology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia 23298 2Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065 Correspondence: [email protected] The Eph and Tie cell surface receptors mediate a variety of signaling events during develop- ment and in the adult organism. As other receptor tyrosine kinases, they are activated on binding of extracellular ligands and their catalytic activity is tightly regulated on multiple levels. The Eph and Tie receptors display some unique characteristics, including the require- ment of ligand-induced receptor clustering for efficient signaling. Interestingly, both Ephs and Ties can mediate different, even opposite, biological effects depending on the specific ligand eliciting the response and on the cellular context. Here we discuss the structural features of these receptors, their interactions with various ligands, as well as functional implications for downstream signaling initiation. The Eph/ephrin structures are already well reviewed and we only provide a brief overview on the initial binding events. We go into more detail discussing the Tie-angiopoietin structures and recognition. ANGIOPOIETINS AND TIE2 In contrast tovasculogenesis, angiogenesis is asculogenesis and angiogenesis are distinct continually required in the adult for wound re- Vcellular processes essential to the creation of pairand remodeling of reproductive tissues dur- the adult vasculature. In early embryonic devel- ing female menstruation.
    [Show full text]
  • Structural Basis of Tie2 Activation and Tie2/Tie1 Heterodimerization
    Structural basis of Tie2 activation and Tie2/Tie1 heterodimerization Veli-Matti Leppänena,1, Pipsa Saharinena,b, and Kari Alitaloa,b,1 aWihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland; and bTranslational Cancer Biology Program, Research Programs Unit, University of Helsinki, 00014 Helsinki, Finland Contributed by Kari Alitalo, March 8, 2017 (sent for review September 28, 2016; reviewed by Joseph Schlessinger and Michel O. Steinmetz) The endothelial cell (EC)-specific receptor tyrosine kinases mice lacking Tie1 develop severe edema around E13.5 because Tie1 and Tie2 are necessary for the remodeling and maturation of compromised microvessel integrity and defects in lymphatic of blood and lymphatic vessels. Angiopoietin-1 (Ang1) growth vasculature and die subsequently (15, 16). Furthermore, Tie1 has factor is a Tie2 agonist, whereas Ang2 functions as a context- critical functions in vascular pathologies, e.g., in tumor angio- dependent agonist/antagonist. The orphan receptor Tie1 modu- genesis and atherosclerosis progression (12, 17). lates Tie2 activation, which is induced by association of angio- In EC monolayers, angiopoietins stimulate Tie receptor trans- cis – trans location to cell–cell junctions for Tie2 trans-association, whereas poietins with Tie2 in and across EC EC junctions in . – Except for the binding of the C-terminal angiopoietin domains in the absence of cell cell adhesion the Tie receptors are an- to the Tie2 ligand-binding domain, the mechanisms for Tie2 chored to the extracellular matrix (ECM) by Ang1-induced Tie2 cis-association (10, 18). Integrins also have been implicated in activation are poorly understood. We report here the structural α β – basis of Ang1-induced Tie2 dimerization in cis and provide Tie2 signaling, and the 5 1 integrin heterodimer enhances Ang1-induced EC adhesion and Tie2 activation (13, 19, 20).
    [Show full text]
  • Additional File 3
    Sustaining Proliferative Signaling Evading Growth Suppressors -log10 -log10 pval pval ERK Cascade ( B Cell Receptor Signaling Cyclin E Associated Events During G1/S T 15 ERK Cascade ( CD4 T Cell Receptor Signal Inhibition Of Replication Initiation Of 15 Intracellular Signalling Through Adenosi ARMS Mediated Activation Cyclin A:Cdk2 Associated Events At S Pha Heterotrimeric GPCR Signaling Pathway (t Negative Regulation Of The PI3K/AKT Netw CREB Phosphorylation Through The Activat 10 APC Truncation Mutants Have Impaired AXI 10 Frs2 Mediated Activation Tetrachlorodibenzodioxin Inhibits The Re ERK Cascade ( FGF8 Signaling (Mouse) )// Spry Regulation Of FGF Signaling Negative Regulation Of (transcription By PTK6 Regulates RHO GTPases, RAS GTPase A Gene Expression Of Smad6/7 By R Smad:sma 5 5 Regulation Of RAS By GAPs SMAD2/SMAD3:SMAD4 Heterotrimer Regulates FCERI Mediated MAPK Activation Downregulation Of SMAD2/3:SMAD4 Transcri MAP2K And MAPK Activation MTOR Signaling Pathway TGF Beta Receptor Signaling Activates SM EGF Signaling Pathway ( EGF Signaling Pa 0 Cyclin D Associated Events In G1 0 GRB2 Events In EGFR Signaling// SHC1 Eve P53 Dependent G1 DNA Damage Response Signalling To P38 Via RIT And RIN TGF Beta Receptor Signaling In EMT (epit P38MAPK Events Activation Of RAS In B Cells AUF1 (hnRNP D0) Binds And Destabilizes M Raf Activation Signaling (through RasGRP Direct P53 Effectors RAF Activation TGF Beta Receptor Trk Receptor Signaling Mediated By The M P53 Pathway Feedback Loops 2 Negative Regulation Of MAPK Pathway Ras Signaling In
    [Show full text]