Implication of Netrin-1 Gain of Expression in Canine Nodal Lymphoma
Netrin-1 is a member of the laminin superfamily, and is known to interact with specific receptors, called dependence receptors. While upon netrin-1 binding these receptors initiate positive signaling, in absence of netrin-1, these receptors trigger apoptosis. Tumor cells can avoid apoptosis by inact...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Veterinary Sciences |
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| Online Access: | https://www.mdpi.com/2306-7381/9/9/494 |
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| author | Antonin Tortereau Nadège Milhau Elodie Rhumy Marie Castets Frédérique Ponce Patrick Mehlen Thierry Marchal |
| author_facet | Antonin Tortereau Nadège Milhau Elodie Rhumy Marie Castets Frédérique Ponce Patrick Mehlen Thierry Marchal |
| author_sort | Antonin Tortereau |
| collection | DOAJ |
| description | Netrin-1 is a member of the laminin superfamily, and is known to interact with specific receptors, called dependence receptors. While upon netrin-1 binding these receptors initiate positive signaling, in absence of netrin-1, these receptors trigger apoptosis. Tumor cells can avoid apoptosis by inactivating these receptors or by gaining ligand expression. The aim of the present study was to investigate the expression of netrin-1, the ligand of dependence receptors, in canine healthy lymph nodes (LN), and in lymphomas and to evaluate efficiency of a netrin-1 interfering compound in cell cultures from canine lymphoma. Thirty-two control LN and 169 lymphomas were analyzed through immunohistochemistry. Netrin-1 was expressed in the nucleoli of lymphoid and non-lymphoid cells in controls. Acquisition of a cytoplasmic expression was present in B-cell lymphomas (23.1 % in low-grade and 50.6% in high-grade) and T-cell lymphomas (50.0 % in low-grade and 78.8 % in high-grade), with a significant difference between the high- and low-grade in B-cell lymphomas. Through flow cytometry, we showed a significant increase in netrin-1 expression in either high-grade B-cell and T-cell lymphomas (19 and 5, respectively) compared with healthy LN (5), likewise an RT-qPCR analysis demonstrated a significant increase in netrin-1 expression level in 14 samples of lymphomas compared with eight samples of healthy LN. A T-cell aggressive canine lymphoma cell line and four primary canine nodal lymphomas cell cultures were treated with a netrin-1 interfering antibody. Apoptosis by measuring caspase 3 activity was significantly increased in the cell line and viability was decreased in three of the four primary cell cultures. Together, these data suggest that netrin-1 expression is increased in lymphoma, and more specifically in high-grade lymphomas, and that netrin-1 can act as a survival factor for the neoplastic cells, and so be a therapeutic target. |
| first_indexed | 2024-03-09T22:15:44Z |
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| institution | Directory Open Access Journal |
| issn | 2306-7381 |
| language | English |
| last_indexed | 2024-03-09T22:15:44Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | Veterinary Sciences |
| spelling | doaj.art-df3b5d9b63334e44bf96d07fc09af0392023-11-23T19:24:22ZengMDPI AGVeterinary Sciences2306-73812022-09-019949410.3390/vetsci9090494Implication of Netrin-1 Gain of Expression in Canine Nodal LymphomaAntonin Tortereau0Nadège Milhau1Elodie Rhumy2Marie Castets3Frédérique Ponce4Patrick Mehlen5Thierry Marchal6Université de Lyon, VetAgro Sup, Interactions Cellules Environnement, ICE, 69280 Marcy l’Etoile, FranceUniversité de Lyon, VetAgro Sup, Interactions Cellules Environnement, ICE, 69280 Marcy l’Etoile, FranceUniversité de Lyon, VetAgro Sup, Interactions Cellules Environnement, ICE, 69280 Marcy l’Etoile, FranceChildhood Cancer & Cell Death (C3), Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon (CRCL), 69008 Lyon, FranceUniversité de Lyon, VetAgro Sup, Interactions Cellules Environnement, ICE, 69280 Marcy l’Etoile, FranceApoptosis, Cancer and Development Laboratory—Equipe labellisée ‘La Ligue’, LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon 1, Centre Léon Bérard, 69008 Lyon, FranceUniversité de Lyon, VetAgro Sup, Interactions Cellules Environnement, ICE, 69280 Marcy l’Etoile, FranceNetrin-1 is a member of the laminin superfamily, and is known to interact with specific receptors, called dependence receptors. While upon netrin-1 binding these receptors initiate positive signaling, in absence of netrin-1, these receptors trigger apoptosis. Tumor cells can avoid apoptosis by inactivating these receptors or by gaining ligand expression. The aim of the present study was to investigate the expression of netrin-1, the ligand of dependence receptors, in canine healthy lymph nodes (LN), and in lymphomas and to evaluate efficiency of a netrin-1 interfering compound in cell cultures from canine lymphoma. Thirty-two control LN and 169 lymphomas were analyzed through immunohistochemistry. Netrin-1 was expressed in the nucleoli of lymphoid and non-lymphoid cells in controls. Acquisition of a cytoplasmic expression was present in B-cell lymphomas (23.1 % in low-grade and 50.6% in high-grade) and T-cell lymphomas (50.0 % in low-grade and 78.8 % in high-grade), with a significant difference between the high- and low-grade in B-cell lymphomas. Through flow cytometry, we showed a significant increase in netrin-1 expression in either high-grade B-cell and T-cell lymphomas (19 and 5, respectively) compared with healthy LN (5), likewise an RT-qPCR analysis demonstrated a significant increase in netrin-1 expression level in 14 samples of lymphomas compared with eight samples of healthy LN. A T-cell aggressive canine lymphoma cell line and four primary canine nodal lymphomas cell cultures were treated with a netrin-1 interfering antibody. Apoptosis by measuring caspase 3 activity was significantly increased in the cell line and viability was decreased in three of the four primary cell cultures. Together, these data suggest that netrin-1 expression is increased in lymphoma, and more specifically in high-grade lymphomas, and that netrin-1 can act as a survival factor for the neoplastic cells, and so be a therapeutic target.https://www.mdpi.com/2306-7381/9/9/494nodal lymphomadognetrin-1dependence receptorsimmunotherapy |
| spellingShingle | Antonin Tortereau Nadège Milhau Elodie Rhumy Marie Castets Frédérique Ponce Patrick Mehlen Thierry Marchal Implication of Netrin-1 Gain of Expression in Canine Nodal Lymphoma Veterinary Sciences nodal lymphoma dog netrin-1 dependence receptors immunotherapy |
| title | Implication of Netrin-1 Gain of Expression in Canine Nodal Lymphoma |
| title_full | Implication of Netrin-1 Gain of Expression in Canine Nodal Lymphoma |
| title_fullStr | Implication of Netrin-1 Gain of Expression in Canine Nodal Lymphoma |
| title_full_unstemmed | Implication of Netrin-1 Gain of Expression in Canine Nodal Lymphoma |
| title_short | Implication of Netrin-1 Gain of Expression in Canine Nodal Lymphoma |
| title_sort | implication of netrin 1 gain of expression in canine nodal lymphoma |
| topic | nodal lymphoma dog netrin-1 dependence receptors immunotherapy |
| url | https://www.mdpi.com/2306-7381/9/9/494 |
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