Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo
Background Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), increases survival in patients with advanced EGFR-positive non-small cell lung cancer when administrated in combination with chemotherapy. In this study, we investigated the role of complement activation in the...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2010 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/13051 |
| Acceso en línea: | https://hdl.handle.net/10171/13051 |
| Access Level: | acceso abierto |
| Palabra clave: | Tumor markers Lung cancer Bronchoalveolar lavage Sputum Complement factor H Diagnosis |
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Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivoHsu, Y.F. (Y. F.)|||/items/eb97868a-362c-48e1-b754-f75ffccfe15aAjona, D. (Daniel)|||/items/33f1d5ec-5a97-4d7f-a428-499e5075fc78Corrales, L. (Leticia)|||/items/25c2d48d-8ffb-42b9-adab-dd66b9660e88Lopez-Picazo, J.M. (José María)|||/items/1a2fbd26-96ec-4587-b2d2-8f6ea1f707deGurpide-Ayarra, L.A. (Luis Alfonso)|||/items/0935e09d-b036-414b-ac0f-688dbfa94d7fMontuenga-Badia, L.M. (Luis M.)|||/items/4c999705-b2c9-45ac-ba13-3f18594ae596Pio, R. (Rubén)|||/items/d5c409b3-dbed-4f0c-8bad-94c31e0e5a95Tumor markersLung cancerBronchoalveolar lavageSputumComplement factor HDiagnosisBackground Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), increases survival in patients with advanced EGFR-positive non-small cell lung cancer when administrated in combination with chemotherapy. In this study, we investigated the role of complement activation in the antitumor mechanism of this therapeutic drug. Results EGFR-expressing lung cancer cell lines were able to bind cetuximab and initiate complement activation by the classical pathway, irrespective of the mutational status of EGFR. This activation led to deposition of complement components and increase in complement-mediated cell death. The influence of complement activation on the activity of cetuximab in vivo was evaluated in xenografts of A549 lung cancer cells on nude mice. A549 cells express wild-type EGFR and have a KRAS mutation. Cetuximab activity against A549 xenografts was highly dependent on complement activation, since complement depletion completely abrogated the antitumor efficacy of cetuximab. Moreover, cetuximab activity was significantly higher on A549 cells in which a complement inhibitor, factor H, was genetically downregulated. Conclusions We demonstrate for the first time that the in vivo antitumor activity of cetuximab can be associated with a complement-mediated immune response. These results may have important implications for the development of new cetuximab-based therapeutic strategies and for the identification of markers that predict clinical response.Biomed CentralDadun. Depósito Académico Digital Universidad de Navarra20102010-09-2920102010-06-0120102010-06-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/13051reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/130512026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo |
| title |
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo |
| spellingShingle |
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo Hsu, Y.F. (Y. F.)|||/items/eb97868a-362c-48e1-b754-f75ffccfe15a Tumor markers Lung cancer Bronchoalveolar lavage Sputum Complement factor H Diagnosis |
| title_short |
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo |
| title_full |
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo |
| title_fullStr |
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo |
| title_full_unstemmed |
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo |
| title_sort |
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo |
| dc.creator.none.fl_str_mv |
Hsu, Y.F. (Y. F.)|||/items/eb97868a-362c-48e1-b754-f75ffccfe15a Ajona, D. (Daniel)|||/items/33f1d5ec-5a97-4d7f-a428-499e5075fc78 Corrales, L. (Leticia)|||/items/25c2d48d-8ffb-42b9-adab-dd66b9660e88 Lopez-Picazo, J.M. (José María)|||/items/1a2fbd26-96ec-4587-b2d2-8f6ea1f707de Gurpide-Ayarra, L.A. (Luis Alfonso)|||/items/0935e09d-b036-414b-ac0f-688dbfa94d7f Montuenga-Badia, L.M. (Luis M.)|||/items/4c999705-b2c9-45ac-ba13-3f18594ae596 Pio, R. (Rubén)|||/items/d5c409b3-dbed-4f0c-8bad-94c31e0e5a95 |
| author |
Hsu, Y.F. (Y. F.)|||/items/eb97868a-362c-48e1-b754-f75ffccfe15a |
| author_facet |
Hsu, Y.F. (Y. F.)|||/items/eb97868a-362c-48e1-b754-f75ffccfe15a Ajona, D. (Daniel)|||/items/33f1d5ec-5a97-4d7f-a428-499e5075fc78 Corrales, L. (Leticia)|||/items/25c2d48d-8ffb-42b9-adab-dd66b9660e88 Lopez-Picazo, J.M. (José María)|||/items/1a2fbd26-96ec-4587-b2d2-8f6ea1f707de Gurpide-Ayarra, L.A. (Luis Alfonso)|||/items/0935e09d-b036-414b-ac0f-688dbfa94d7f Montuenga-Badia, L.M. (Luis M.)|||/items/4c999705-b2c9-45ac-ba13-3f18594ae596 Pio, R. (Rubén)|||/items/d5c409b3-dbed-4f0c-8bad-94c31e0e5a95 |
| author_role |
author |
| author2 |
Ajona, D. (Daniel)|||/items/33f1d5ec-5a97-4d7f-a428-499e5075fc78 Corrales, L. (Leticia)|||/items/25c2d48d-8ffb-42b9-adab-dd66b9660e88 Lopez-Picazo, J.M. (José María)|||/items/1a2fbd26-96ec-4587-b2d2-8f6ea1f707de Gurpide-Ayarra, L.A. (Luis Alfonso)|||/items/0935e09d-b036-414b-ac0f-688dbfa94d7f Montuenga-Badia, L.M. (Luis M.)|||/items/4c999705-b2c9-45ac-ba13-3f18594ae596 Pio, R. (Rubén)|||/items/d5c409b3-dbed-4f0c-8bad-94c31e0e5a95 |
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author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Tumor markers Lung cancer Bronchoalveolar lavage Sputum Complement factor H Diagnosis |
| topic |
Tumor markers Lung cancer Bronchoalveolar lavage Sputum Complement factor H Diagnosis |
| description |
Background Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), increases survival in patients with advanced EGFR-positive non-small cell lung cancer when administrated in combination with chemotherapy. In this study, we investigated the role of complement activation in the antitumor mechanism of this therapeutic drug. Results EGFR-expressing lung cancer cell lines were able to bind cetuximab and initiate complement activation by the classical pathway, irrespective of the mutational status of EGFR. This activation led to deposition of complement components and increase in complement-mediated cell death. The influence of complement activation on the activity of cetuximab in vivo was evaluated in xenografts of A549 lung cancer cells on nude mice. A549 cells express wild-type EGFR and have a KRAS mutation. Cetuximab activity against A549 xenografts was highly dependent on complement activation, since complement depletion completely abrogated the antitumor efficacy of cetuximab. Moreover, cetuximab activity was significantly higher on A549 cells in which a complement inhibitor, factor H, was genetically downregulated. Conclusions We demonstrate for the first time that the in vivo antitumor activity of cetuximab can be associated with a complement-mediated immune response. These results may have important implications for the development of new cetuximab-based therapeutic strategies and for the identification of markers that predict clinical response. |
| publishDate |
2010 |
| dc.date.none.fl_str_mv |
2010 2010-09-29 2010 2010-06-01 2010 2010-06-01 |
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journal article http://purl.org/coar/resource_type/c_6501 |
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info:eu-repo/semantics/article |
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article |
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https://hdl.handle.net/10171/13051 |
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https://hdl.handle.net/10171/13051 |
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Inglés eng |
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Inglés |
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eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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Biomed Central |
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Biomed Central |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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