View Abstract

A7518 - Mechanical Ventilation Promotes the Spread of Tumor Cell from the Lungs
Author Block: I. López-Alonso1, C. López-Martínez2, C. Huidobro1, L. Amado-Rodriguez1, J. Blázquez-Prieto3, G. M. Albaiceta4; 1Instituto de Investigacion Sanitaria del Principado de Asturias, Oviedo, Spain, 2Departamento de Biología Funcional, Universidad de Oviedo, Oviedo, Spain, 3CIBER-Enfermedades Respiratorias, Madrid, Spain, 4Cardiac Intensive Care Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.
Rationale: The application of positive pressure ventilation triggers both local and systemic responses, including inflammation, matrix remodeling and promotion of apoptosis. Interestingly, all these processes have been related to tumor progression. The aim of this study is to characterize the impact of mechanical ventilation in cancer progression. Methods: Twelve weeks old C57Bl/6 mice were injected (via jugular vein or spleen) with luciferase-transfected B16F10 melanoma cells to induce lung or liver tumors respectively. Medium-injected animals were used as controls. Two weeks after injection, mice were anesthetized and randomly grouped to spontaneous breathing or mechanical ventilation for 150 minutes. After ventilation, animals were extubated and followed for two additional weeks. At the end of the follow-up, mice were sacrificed and tissues sampled. Micrometastases were diagnosed by detection of luciferase by qPCR. Cultured B16F10 cells were submitted to mechanical stretch (15% equibiaxial elongation), both cells and supernatants collected, and their invasive potential studied in Matrigel chambers. Gene expression in cultured cells was studied by qPCR. In addition gelatin zimographies were performed in order to determine the secretion of MMP2 and MMP9. Results: Animals with lung tumor submitted to mechanical ventilation showed an increase in brain (47 vs 14%, p=0.01) and kidney (47 vs 25%, p=0.05) micrometastases compared to their non-ventilated counterparts. However, there were no differences in systemic spread in animals with liver tumors. No tumors were detected in medium-injected animals. Mechanical stretch of cultured cells increased 2.5 fold their invasiveness through matrigel chambers. Adding supernatants from stretched cells led to a slight additional increase in invasiveness. Gene expression in cells showed an pro-invasive reprograming after mechanical stretch. In addition cells secreted higher levels of MMP2 and MMP9 among others in response to mechanical stimulation, favouring a prometastatic environment. Conclusion: Mechanical ventilation facilitates the systemic spread of lung tumors by a direct effect of stretch on invasiveness of tumor cells.