Inhibition of the colony-stimulating-factor-1 receptor affects the resistance of lung cancer cells to cisplatin

摘要: // Harvey I. Pass 1 , Carmencita Lavilla 2 Claudia Canino 1, 5 Chandra Goparaju Jordan Preiss Samrah Noreen Giovanni Blandino 3, 4 Mario Cioce 3 Division of Thoracic Surgery, Department Cardiothoracic Langone Medical Center, New York University, York, USA University Translational Oncogenomics Unit, Italian National Cancer Institute 'Regina Elena', Rome, Italy Oncology, Juravinski Center-McMaster Hamilton, Ontario, Canada Campus Biomedico, Correspondence to: Cioce, email: mario.cioce@ifo.gov.it Keywords: lung cancer, chemoresistance, CSF-1, CSF-1R, ALDH Received: May 10, 2016      Accepted: June 30, Published: July 28, 2016 ABSTRACT In the present work we show that multiple cancer cell lines contain cisplatin resistant subpopulations expressing Colony-Stimulating-Factor-Receptor-1 (CSF-1R) and surviving chemotherapy-induced stress. By exploiting siRNA-mediated knock down in vitro use an investigational CSF-1R TKI (JNJ-40346527) vivo expression function receptor are required for clonogenicity chemoresistance lines. Thus, inhibition kinase activity reduced levels EMT-associated genes, stem markers genes. Additionally, number high aldehyde dehydrogenase (ALDH) cells was reduced, consequent to lack cisplatin-induced increase isoforms. This affected collective treated cultures. Treatment tumor bearing mice with JNJ-40346527, at pharmacologically relevant doses, produced strong chemo-sensitizing effects . These anticancer correlated a pos cells, tumors excised from mice. Depletion CD45 within did not, apparently, play major role mediating therapeutic response TKI. express functional CSF-1 duo which mediates pro-tumorigenic can be targeted therapeutically way. observations complement already known properties tumor-infiltrating immune components.