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1. Role of CD146 (MCAM) in Physiological and Pathological Angiogenesis—Contribution of New Antibodies for Therapy

Author

Joshkon, Ahmad, Heim, Xavier, Dubrou, Cléa, Bachelier, Richard, Traboulsi, Wael, STALIN, JIMMY, Fayyad-Kazan, Hussein, Badran, Bassam, Foucault-Bertaud, Alexandrine, Leroyer, Aurélie, Bardin, Nathalie, Blot-Chabaud, Marcel, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lebanese International University (LIU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), This work was financially supported by Inserm, Aix-Marseille University, and MSD Avenir., Hôpital de la Timone [CHU - APHM] (TIMONE), Lebanese University [Beirut] (LU), Leroyer, Aurelie, Lucas, Nelly, Faculty of Sciences [Lebanese University] | Faculté des Sciences [Université Libanaise], and Faculty of Sciences [Lebanese University]

Subjects
[SDV] Life Sciences [q-bio], angiogenesis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, lcsh:Biology (General), CD146, inflammation, [SDV]Life Sciences [q-bio], endothelial cell, cancer, Review, monoclonal antibodies, lcsh:QH301-705.5, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; The fundamental role of cell adhesion molecules in mediating various biological processes as angiogenesis has been well-documented. CD146, an adhesion molecule of the immunoglobulin superfamily, and its soluble form, constitute major players in both physiological and pathological angiogenesis. A growing body of evidence shows soluble CD146 to be significantly elevated in the serum or interstitial fluid of patients with pathologies related to deregulated angiogenesis, as autoimmune diseases, obstetric and ocular pathologies, and cancers. To block the undesirable effects of this molecule, therapeutic antibodies have been developed. Herein, we review the multifaceted functions of CD146 in physiological and pathological angiogenesis and summarize the interest of using monoclonal antibodies for therapeutic purposes.

Published
2020
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2. A novel anti-CD146 antibody specifically targets cancer cells by internalizing the molecule

Author

Nollet, Marie, STALIN, JIMMY, Moyon, Anaïs, Traboulsi, Wael, Essaadi, Amel, Robert, Stéphane, Malissen, Nausicaa, Bachelier, Richard, Daniel, Laurent, Foucault-Bertaud, Alexandrine, Gaudy-Marqueste, Caroline, Lacroix, Romaric, Leroyer, Aurélie, Guillet, Benjamin, Bardin, Nathalie, Dignat-George, Francoise, Blot-Chabaud, Marcel, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de l'Endothelium, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Département de dermatologie [CHU de Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Timone [CHU - APHM] (TIMONE), Département de dermatologie, CHU Marseille, CHU Marseille, Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )

Subjects
therapy, PET, CD146, antibody, [SDV]Life Sciences [q-bio], cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; CD146 is an adhesion molecule present on many tumors (melanoma, kidney, pancreas, breast, ...). In addition, it has been shown to be expressed on vascular endothelial and smooth muscle cells. Generating an antibody able to specifically recognize CD146 in cancer cells (designated as tumor CD146), but not in normal cells, would thus be of major interest for targeting tumor CD146 without affecting the vascular system. We thus generated antibodies against the extracellular domain of the molecule produced in cancer cells and selected an antibody that specifically recognizes tumor CD146. This antibody (TsCD146 mAb) was able to detect CD146-positive tumors in human biopsies and in vivo, by PET imaging, in a murine xenograft model. In addition, TsCD146 mAb antibody was able to specifically detect CD146-positive cancer microparticles in the plasma of patients. TsCD146 mAb displayed also therapeutic effects since it was able to reduce the growth of human CD146-positive cancer cells xenografted in nude mice. This effect was due to a decrease in the proliferation and an increase in the apoptosis of CD146-positive cancer cells after TsCD146-mediated internalization of the cell surface CD146. Thus, TsCD146 mAb could be of major interest for diagnostic and therapeutic strategies against CD146-positive tumors in a context of personalized medicine. www.impactjournals.com/oncotarget/

Published
2017
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4. Consensus guidelines for the use and interpretation of angiogenesis assays

Author

Nowak-Sliwinska, Patrycja, Alitalo, Kari, Allen, Elizabeth, Anisimov, Andrey, Aplin, Alfred C, Auerbach, Robert, Augustin, Hellmut G, Bates, David O, van Beijnum, Judy R, Bender, R Hugh F, Bergers, Gabriele, Bikfalvi, Andreas, Bischoff, Joyce, Böck, Barbara C, Brooks, Peter C, Bussolino, Federico, Cakir, Bertan, Carmeliet, Peter, Castranova, Daniel, Cimpean, Anca M, Cleaver, Ondine, Coukos, George, Davis, George E, De Palma, Michele, Dimberg, Anna, Dings, Ruud P M, Djonov, Valentin, Dudley, Andrew C, Dufton, Neil P, Fendt, Sarah-Maria, Ferrara, Napoleone, Fruttiger, Marcus, Fukumura, Dai, Ghesquière, Bart, Gong, Yan, Griffin, Robert J, Harris, Adrian L, Hughes, Christopher C W, Hultgren, Nan W, Iruela-Arispe, M Luisa, Irving, Melita, Jain, Rakesh K, Kalluri, Raghu, Kalucka, Joanna, Kerbel, Robert S, Kitajewski, Jan, Klaassen, Ingeborg, Kleinmann, Hynda K, Koolwijk, Pieter, Kuczynski, Elisabeth, Kwak, Brenda R, Marien, Koen, Melero-Martin, Juan M, Munn, Lance L, Nicosia, Roberto F, Noel, Agnes, Nurro, Jussi, Olsson, Anna-Karin, Petrova, Tatiana V, Pietras, Kristian, Pili, Roberto, Pollard, Jeffrey W, Post, Mark J, Quax, Paul H A, Rabinovich, Gabriel A, Raica, Marius, Randi, Anna M, Ribatti, Domenico, Ruegg, Curzio, Schlingemann, Reinier O, Schulte-Merker, Stefan, Smith, Lois E H, Song, Jonathan W, Stacker, Steven A, Stalin, Jimmy, Stratman, Amber N, Van de Velde, Maureen, van Hinsbergh, Victor W M, Vermeulen, Peter B, Waltenberger, Johannes, Weinstein, Brant M, Xin, Hong, Yetkin-Arik, Bahar, Yla-Herttuala, Seppo, Yoder, Mervin C, and Griffioen, Arjan W

Subjects
3. Good health
Abstract

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

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