| Added by | celine.gongora |
|---|---|
| Group name | EquipeCG |
| Item Type | Journal Article |
| Title | Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis |
| Creator | Leconet et al. |
| Author | Wilhem Leconet |
| Author | Myriam Chentouf |
| Author | Stanislas du Manoir |
| Author | Clément Chevalier |
| Author | Audrey Sirvent |
| Author | Imade Aït-Arsa |
| Author | Muriel Busson |
| Author | Marta Jarlier |
| Author | Nina Radosevic-Robin |
| Author | Charles Theillet |
| Author | Dany Chalbos |
| Author | Jean-Max Pasquet |
| Author | André Pèlegrin |
| Author | Christel Larbouret |
| Author | Bruno Robert |
| Abstract | Purpose: AXL receptor tyrosine kinase has been described as a relevant molecular marker and a key player in invasiveness, especially in triple-negative breast cancer (TNBC).Experimental Design: We evaluate the antitumor efficacy of the anti-AXL monoclonal antibody 20G7-D9 in several TNBC cell xenografts or patient-derived xenograft (PDX) models and decipher the underlying mechanisms. In a dataset of 254 basal-like breast cancer samples, genes correlated with AXL expression are enriched in EMT, migration, and invasion signaling pathways.Results: Treatment with 20G7-D9 inhibited tumor growth and bone metastasis formation in AXL-positive TNBC cell xenografts or PDX, but not in AXL-negative PDX, highlighting AXL role in cancer growth and invasion. In vitro stimulation of AXL-positive cancer cells by its ligand GAS6 induced the expression of several EMT-associated genes (SNAIL, SLUG, and VIM) through an intracellular signaling implicating the transcription factor FRA-1, important in cell invasion and plasticity, and increased their migration/invasion capacity. 20G7-D9 induced AXL degradation and inhibited all AXL/GAS6-dependent cell signaling implicated in EMT and in cell migration/invasion.Conclusions: The anti-AXL antibody 20G7-D9 represents a promising therapeutic strategy in TNBC with mesenchymal features by inhibiting AXL-dependent EMT, tumor growth, and metastasis formation. Clin Cancer Res; 23(11); 2806-16. ©2016 AACR. |
| Publication | Clinical Cancer Research: An Official Journal of the American Association for Cancer Research |
| Volume | 23 |
| Issue | 11 |
| Pages | 2806-2816 |
| Date | Jun 01, 2017 |
| Journal Abbr | Clin. Cancer Res. |
| Language | eng |
| DOI | 10.1158/1078-0432.CCR-16-1316 |
| ISSN | 1078-0432 |
| Library Catalog | PubMed |
| Extra | PMID: 27923843 |
| Tags | Animals, Antibodies, Anti-Idiotypic, Cell Movement, Cell Proliferation, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Heterografts, Humans, ipam, mabimprove, Mice, Neoplasm Metastasis, oRIBASE PHARMA, original, PDX, phd, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Signal Transduction, Triple Negative Breast Neoplasms, Xenograft Model Antitumor Assays |
| Date Added | 2019/05/14 - 11:58:26 |
| Date Modified | 2019/10/24 - 16:41:37 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
