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

• Applicant: Dr. Nina Linde
• Subject Area: Cell Biology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 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 bedependent 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 metastasis formation. Macrophages are a versatile cell population able to differentiate into different subtypes 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. Thereby, 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 Programme: Research Fellowships
• International Connection: USA
• Host: Professor Julio Aguirre-Ghiso, Ph.D.