The Metastatic Microenvironment

Metastasis is the major killer of cancer patients. Although increased understanding of the metastatic process was achieved in recent years, the mechanisms underlying the progression of cancer cells to form site-specific metastasis are still awaiting complete elucidation. The current consensus is that circulating tumor cells disseminate into future metastatic sites and that these disseminated tumor cells form micrometastasis in these sites. The micrometastases remain in a state of dormancy in these sites until ‘‘awakened’’ to progress towards overt metastases. Whereas the evidence implicating chemokine–chemokine receptor interactions as the mechanism responsible for the targeted migration of tumor cells to future metastatic sites is quite strong, the mechanisms that maintain dormancy of disseminated tumor cells and the mechanisms that awaken these dormant micrometastases, driving their progression towards frank metastasis, are still obscure. It is clear, however, that the metastatic microenvironment plays a major role in these events. Three topics are discussed in this review: Mechanisms that are involved in the targeted migration of tumor cells to future metastatic sites; Specific molecular signatures expressed by metastases and micrometastases and interactions between metastatic and micrometastatic cells with the metastatic microenvironment. In reviewing these topics we focused on studies performed in our lab with neuroblatoma lung and melanoma brain metastasis. S. Maman I. P. Witz Department of Cell Research and Immunology George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel S. Maman I. P. Witz Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA I. P. Witz (&) Department of Cell Research and Immunology George S, Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel e-mail: [email protected] M. R. Shurin et al. (eds.), The Tumor Immunoenvironment, DOI: 10.1007/978-94-007-6217-6_2, Springer Science+Business Media Dordrecht 2013 15