| Added by | mollevi |
|---|---|
| Last modified by | André Pèlegrin |
| Group name | EquipeAP |
| 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 | W. Leconet |
| Author | M. Chentouf |
| Author | C. Chevalier |
| Author | A. Sirevnt |
| Author | I. Ait-Arsa |
| Author | M. Busson |
| Author | M. Jarlier |
| Author | N. Radosevic-Robin |
| Author | C. G. Theillet |
| Author | D. Chalbos |
| Author | J. M. Pasquet |
| Author | A. Pelegrin |
| Author | C. Larbouret |
| Author | B. 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 anti-tumor 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. |
| Publication | Clin Cancer Res |
| Volume | 23 |
| Pages | 2806-2816 |
| Date | 2017 |
| Journal Abbr | Clin Cancer Res |
| DOI | 10.1158/1078-0432.CCR-16-1316 |
| ISSN | 1078-0432 (Print) 1078-0432 (Linking) |
| Tags | Animals, Antibodies, Anti-Idiotypic, Cell Movement, Cell Proliferation, Epithelial-Mesenchymal Transition, Equipe, Female, Gene Expression Regulation, Neoplastic, Heterografts, Humans, Mice, Neoplasm Metastasis, original, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Signal Transduction, top, Triple Negative Breast Neoplasms, Xenograft Model Antitumor Assays |
| Date Added | 2018/07/20 - 10:01:50 |
| Date Modified | 2019/12/19 - 08:49:23 |
| Notes and Attachments | (Note) (Note) (Note) (Note) 27923843 (Attachment) 27923843 (Attachment) |
Institut de Recherche en Cancérologie de
