Abstract B26: Identification of molecular and functional differences in tumor-associated macrophage subsets

Abstract

Abstract During breast cancer metastasis motile tumor cells migrate within the primary tumor to blood vessels and enter the bloodstream which leads these cells to other organs where they can found a new metastasis. These cancer cells have to navigate from their primary site to the blood vessel, and make their way through the extra cellular matrix of the basement membranes of mammary ducts and blood vessels. Cancer cells are not acting alone during the metastatic process. Tumor associated macrophages (TAMs) play an important role during breast cancer development and metastasis. The on-going research aims to gain a better understanding of the origin, location and flexibility in function of different TAM subsets, including the metastasis-assisting macrophages. Using high-resolution multi-photon live-imaging we have identified different TAM subsets based on location and phenotype. For example TAMs can be found at the outside of the tumor (cortical), around tumor blood vessels (perivascular) or in fast moving cell streams (streaming). All these different TAM subsets perform different functions. Cortical TAMs are suggested to be immunosuppressive, while streaming TAMs appear to guide motile cancer cells towards blood vessels, and perivascular macrophages seem to attract the streams and mediate cancer cell intravasation. Currently, there are no (surface) markers to differentiate these unique TAM subsets and little is known about the underlying molecular mechanisms relevant for the differentiation of monocytes into any of these subtypes. The current research is using single-cell laser capture dissection, high-resolution multi-photon live-imaging and lineage tracing experiments to elucidate some aspects of the interplay between cancer cells and macrophages Citation Format: Esther N. Arwert, Allison S. Harney, David Entenberg, Yarong Wang, Jeffrey W. Pollard, John S. Condeelis. Identification of molecular and functional differences in tumor-associated macrophage subsets. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B26.