Interleukin-1β provided by KIT-competent mast cells is required for KRAS-mutant lung adenocarcinoma
| Autor: | Magda Spella, Maria Oplopoiou, Ioannis Lilis, Sebastian Marwitz, Ioanna Giopanou, Vassilios Papaleonidopoulos, Georgios T. Stathopoulos, Antonia Marazioti, Giannoula Ntaliarda, Georgia A. Giotopoulou, Vasiliki Bravou, Torsten Goldmann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Immunology Mutant 1β/lung Cancer/urethane Carboxypeptidase 3/mutation/il Biology medicine.disease_cause lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Carboxypeptidase 3/mutation/IL In vivo medicine Immunology and Allergy Secretion 1β/lung cancer/urethane Gene Original Research Lung medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Molecular biology Interleukin 1β 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Adenocarcinoma KRAS lcsh:RC581-607 |
| Zdroj: | Oncoimmunology OncoImmunology, Vol 8, Iss 7 (2019) OncoImmunology 8:1593802 (2019) |
| ISSN: | 2162-402X 2162-4011 |
| Popis: | Mast cells (MC) have been identified in human lung adenocarcinoma (LADC) tissues, but their functional role has not been investigated in vivo. For this, we applied three mouse models of KRAS-mutant LADC to two different MC-deficient mouse strains (cKitWsh and Cpa3.Cre). Moreover, we derived MC gene signatures from murine bone marrow-derived MC and used them to interrogate five human cohorts of LADC patients. Tumor-free cKitWsh and Cpa3.Cre mice were deficient in alveolar and skin KIT-dependent (KIT+) MC, but cKitWsh mice retained normal KIT-independent (KIT-) MC in the airways. Both KIT+ and KIT- MC infiltrated murine LADC to varying degrees, but KIT+ MC were more abundant and promoted LADC initiation and progression through interleukin-1β secretion. KIT+ MC and their transcriptional signature were significantly enriched in human LADC compared to adjacent normal tissue, especially in the subset of patients with KRAS mutations. Importantly, MC density increased with tumor stage and high overall expression of the KIT+ MC signature portended poor survival. Collectively, our results indicate that KIT+ MC foster LADC development and represent marked therapeutic targets. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|