Acceleration of clear cell renal cell carcinoma growth in mice following bevacizumab/Avastin treatment: the role of CXCL cytokines
| Autor: | Jérôme Durivault, Gilles Pagès, Negrier S, Jean-Yves Scoazec, Chamorey E, Cindy Serdjebi, Marie A. Jacquin, Mélanie Guyot, Lacarelle B, Simonnet H, Sudaka A, Renaud Grépin |
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| Přispěvatelé: | RHODIA RECHERCHES ET TECHNOLOGIES CENTRE DE RECHERCHES ET TECHNOLOGIES D'AUBERVILLIERS, RHODIA RECHERCHES ET TECHNOLOGIES, Biostatistics Unit, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Equipe 4, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research Angiogenesis Inhibitors Mice chemistry.chemical_compound 0302 clinical medicine Antineoplastic Combined Chemotherapy Protocols MESH: Animals MESH: Angiogenesis Inhibitors 0303 health sciences MESH: Carcinoma Renal Cell Kidney Neoplasms 3. Good health Lymphangiogenesis Bevacizumab Vascular endothelial growth factor MESH: Antineoplastic Combined Chemotherapy Protocols Paclitaxel 030220 oncology & carcinogenesis Monoclonal Female medicine.drug Mice Nude [SDV.CAN]Life Sciences [q-bio]/Cancer Biology Antibodies Monoclonal Humanized 03 medical and health sciences In vivo MESH: Cell Proliferation Genetics medicine MESH: Mice Nude Animals Humans MESH: Paclitaxel Carcinoma Renal Cell Molecular Biology MESH: Mice Cell Proliferation 030304 developmental biology MESH: Humans Cell growth MESH: Vascular Endothelial Growth Factor A Interleukin-8 medicine.disease MESH: Interleukin-8 Clear cell renal cell carcinoma chemistry MESH: Antibodies Monoclonal Humanized Immunology Cancer research MESH: Kidney Neoplasms MESH: Female Neoplasm Transplantation MESH: Neoplasm Transplantation |
| Zdroj: | Oncogene Oncogene, 2012, 31 (13), pp.1683-94. ⟨10.1038/onc.2011.360⟩ Oncogene, Nature Publishing Group, 2012, 31 (13), pp.1683-94. ⟨10.1038/onc.2011.360⟩ |
| ISSN: | 0950-9232 1476-5594 |
| DOI: | 10.1038/onc.2011.360⟩ |
| Popis: | International audience; The anti-VEGF targeted antibody bevacizumab (BVZ) has been approved for treating renal cell carcinomas (RCCs). Although BVZ increases the progression-free survival of patients with metastatic RCC, the effect on overall survival is poor. To gain insight into the limited efficacy of BVZ on overall survival, we analyzed patient samples of RCC for angiogenic factors that may participate in escape from anti-VEGF therapy. Our study shows that the level of vascular endothelial growth factor (VEGF) in tumors was increased compared with normal tissue. The level of interleukin-8/CXCL8, a pro-angiogenic member of the CXCL family of cytokines, was also increased in tumors. These observations gave us a good reason to analyze the combined effects of BVZ and anti-CXCL8 antibodies on tumor growth. Surprisingly, we report that BVZ accelerates the growth of RCC in nude mice with in vivo selection of tumor cells with an increased growth capacity. Downregulation of receptor tyrosine phosphatase-κ, a phosphatase implicated in EGF receptor regulation, may partly explain this phenomenon. Modification of the vascular network and development of lymphatic vessels through VEGF-C production and compensatory production of pro-angiogenic CXCL cytokines were also observed. The apparent normalization of the vascular network prompted us to associate BVZ with the chemotherapeutic agent paclitaxel. While efficient in vitro, paclitaxel did not reverse the anti-VEGF effects in vivo. Anti-CXCL8-targeting antibodies were promising as they decreased intra-tumor VEGF production; decreased the pro-angiogenic CXCL/anti-angiogenic CXCL ratio and did not induce lymphangiogenesis. These observations hold clinical implication as they highlight putative markers implicated in escape from BVZ treatment. They also recommend proceeding with caution in the use of anti-VEGF therapy alone for treatment of RCC. |
| Databáze: | OpenAIRE |
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