Next Article in Journal
Preconditioning or Postconditioning with 8-Br-cAMP-AM Protects the Heart against Regional Ischemia and Reperfusion: A Role for Mitochondrial Permeability Transition
Next Article in Special Issue
Mechanisms and Clinical Significance of Tumor Lymphatic Invasion
Previous Article in Journal
Stability across the Whole Nuclear Genome in the Presence and Absence of DNA Mismatch Repair
Previous Article in Special Issue
IFN-λ Modulates the Migratory Capacity of Canine Mammary Tumor Cells via Regulation of the Expression of Matrix Metalloproteinases and Their Inhibitors
Article

Anti-Vascular Endothelial Growth Factor C Antibodies Efficiently Inhibit the Growth of Experimental Clear Cell Renal Cell Carcinomas

1
Département de Biologie Médicale, Centre Scientifique de Monaco, 98000 Monaco, Monaco
2
Institute for Research on Cancer and Aging of Nice, Université Cote d’Azur, CNRS UMR 7284, INSERM U1081, Centre Antoine Lacassagne, 06189 Nice, France
*
Author to whom correspondence should be addressed.
Equally contributed to this work.
Academic Editor: Georg Breier
Cells 2021, 10(5), 1222; https://doi.org/10.3390/cells10051222
Received: 20 April 2021 / Revised: 7 May 2021 / Accepted: 8 May 2021 / Published: 17 May 2021
(This article belongs to the Special Issue Mechanisms of Cancer Cell Invasion)
Despite improvement during the last ten years in the longevity of patients with metastatic clear cell renal cell carcinoma (mccRCC) the disease remains incurable. Hence, new therapeutic strategies are urgently needed. Relapse following anti-angiogenic treatment depends on the over-expression of vascular endothelial growth factor C (VEGFC), one of the main drivers of lymphangiogenesis. Therefore, we developed specific mouse monoclonal antibodies and evaluated their therapeutic efficacy in vitro and in vivo. Immunization of mice with the domain of VEGFC that stimulates the VEGF receptor 3 (VEGFR3) led to the selection of one hybridoma producing specific anti-VEGFC monoclonal antibodies. The selected 1E9 antibodies were sequenced, and the corresponding variable light and heavy chains were subcloned into expression vectors in frame with sequences encoding the human IgG1 constant heavy and light chains. CHO cells were stably transfected and cloned to produce chimeric antibodies. These antibodies inhibited the activation of VEGFR3 signaling, and therefore the proliferation and migration of VEGFC-stimulated endothelial cells. Moreover, they inhibited the proliferation of VEGFC-expressing renal cancer cells through NRP2 signaling. 1E9 antibodies inhibited the growth of experimental RCC, and their therapeutic efficacy was enhanced by the anti-VEGF antibody bevacizumab. Hence, our results suggest that targeting VEGFC could have a relevant therapeutic impact on mccRCC that relapse following anti-angiogenic treatment. View Full-Text
Keywords: angiogenesis; lymphangiogenesis; VEGFC; kidney cancer; resistance to anti-angiogenics angiogenesis; lymphangiogenesis; VEGFC; kidney cancer; resistance to anti-angiogenics
Show Figures

Figure 1

MDPI and ACS Style

Dumond, A.; Montemagno, C.; Vial, V.; Grépin, R.; Pagès, G. Anti-Vascular Endothelial Growth Factor C Antibodies Efficiently Inhibit the Growth of Experimental Clear Cell Renal Cell Carcinomas. Cells 2021, 10, 1222. https://doi.org/10.3390/cells10051222

AMA Style

Dumond A, Montemagno C, Vial V, Grépin R, Pagès G. Anti-Vascular Endothelial Growth Factor C Antibodies Efficiently Inhibit the Growth of Experimental Clear Cell Renal Cell Carcinomas. Cells. 2021; 10(5):1222. https://doi.org/10.3390/cells10051222

Chicago/Turabian Style

Dumond, Aurore, Christopher Montemagno, Valérie Vial, Renaud Grépin, and Gilles Pagès. 2021. "Anti-Vascular Endothelial Growth Factor C Antibodies Efficiently Inhibit the Growth of Experimental Clear Cell Renal Cell Carcinomas" Cells 10, no. 5: 1222. https://doi.org/10.3390/cells10051222

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop