| Added by | André Pèlegrin |
|---|---|
| Group name | EquipeAP |
| Item Type | Journal Article |
| Title | Targeting the NRG1/HER3 pathway in tumor cells and cancer-associated fibroblasts with an anti-neuregulin 1 antibody inhibits tumor growth in pre-clinical models of pancreatic cancer |
| Creator | Ogier et al. |
| Author | Charline Ogier |
| Author | Pierre-Emmanuel Colombo |
| Author | Corinne Bousquet |
| Author | Lucile Canterel-Thouennon |
| Author | Pierre Sicard |
| Author | Véronique Garambois |
| Author | Gaëlle Thomas |
| Author | Nadège Gaborit |
| Author | Marta Jarlier |
| Author | Nelly Pirot |
| Author | Martine Pugnière |
| Author | Nadia Vie |
| Author | Céline Gongora |
| Author | Pierre Martineau |
| Author | Bruno Robert |
| Author | André Pèlegrin |
| Author | Thierry Chardès |
| Author | Christel Larbouret |
| Abstract | Neuregulin 1 (NRG1), a ligand for HER3 and HER4 receptors, is secreted by both pancreatic tumor cells (PC) and cancer-associated fibroblasts (CAFs), the latter representing the most abundant compound of pancreatic stroma. This desmoplastic stroma contributes to Pancreatic Ductal Adenocarcinoma (PDAC) aggressiveness and therapeutic failure by promoting tumor progression, invasion and resistance to chemotherapies. In the present work, we aimed at disrupting the complex crosstalk between PC and CAF in order to prevent tumor cell proliferation. To do so, we demonstrated the promising tumor growth inhibitory effect of the 7E3, an original antibody directed to NRG1. This antibody promotes antibody dependent cellular cytotoxicity in NRG1-positive PC and CAFs and inhibits NRG1-associated signaling pathway induction, by blocking NRG1-mediated HER3 activation. Moreover, 7E3 inhibits migration and growth of pancreatic cancer cells co-cultured with CAFs, both in vitro and in vivo using orthotopic pancreatic tumor xenografts. Our preclinical results demonstrate that the anti-NRG1 antibody 7E3 could represent a promising approach to target pancreatic stroma and cancer cells, thereby providing novel therapeutic options for PDAC. |
| Publication | Cancer Letters |
| Volume | 432 |
| Pages | 227-236 |
| Date | 09 28, 2018 |
| Journal Abbr | Cancer Lett. |
| Language | eng |
| DOI | 10.1016/j.canlet.2018.06.023 |
| ISSN | 1872-7980 |
| Library Catalog | PubMed |
| Extra | 00000 PMID: 29935372 |
| Tags | Animals, Antibodies, Monoclonal, Cancer-associated fibroblast, Carcinoma, Pancreatic Ductal, Cell Proliferation, Coculture Techniques, Equipe, Female, Gene Expression Regulation, Neoplastic, HER3, Humans, Immunotherapy, Mice, Mice, Nude, Neuregulin-1, original, Pancreatic Neoplasms, Receptor, ErbB-3, top, Tumor Cells, Cultured, Tumor Microenvironment, Xenograft Model Antitumor Assays |
| Date Added | 2019/09/12 - 09:42:42 |
| Date Modified | 2019/12/11 - 18:32:36 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
