Target organ specific influences of macrophages on dormancy of disseminated tumorcells.

• Antragstellerin: Dr. Nina Linde
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2012 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 226053574

Metastatic relapse can occur years or decades after removal of the primary tumor, indicating that disseminated tumor cells (DTCs) can persist in a dormant state and eventually reach a proliferative state again. Whether DTCs become dormant or start proliferating and form metastases seems to be dependent on the specific microenvironment in their target organ: dormant DTCs are commonly detected in the bone, whereas DTCs in the lung rather start proliferating and develop into metastatic lesions. This implies a regulatory function of cells of the microenvironment on metastatic growth.Tumor-associated macrophages play an important role in primary tumor development as well as me-tastasis formation. Macrophages are a versatile cell population able to differentiate into different sub-types and they can have opposing effects on tumor progression depending on their polarizationstatus. This indicates that macrophages provide a microenvironmental switch. We hypothesize that the activation status of macrophages is crucial for the decision whether DTCs reach a dormant or a proliferative state. We will compare the influence of resident bone and alveolar macrophages ondormancy of DTCs in the murine MMTV-Neu model of spontaneous mammary carcinogenesis. There-by, we seek to identify microenvironment specific differences of the mechanisms underlying dormancy and ultimately aim to identify factors involved in the induction and interruption of dormancy.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeber: Professor Julio Aguirre-Ghiso, Ph.D.