Imaging interactions between macrophages and tumour cells that are involved in metastasis in vivo and in vitro

Tumour-associated macrophages participate in several protumour functions including tumour growth and angiogenesis, and facilitate almost every step of the metastatic cascade. Interfering with macrophage functions may therefore provide an important strategy in the clinical management of cancer and metastatic disease. Our understanding of macrophage functions has been greatly expanded by direct observations of macrophage-carcinoma cell interactions using light microscopy. Imaging approaches include intravital microscopy of tumours in mouse models of cancer and visualization of macrophage-carcinoma cell interactions in in vitro assays; whether atop 2D substrates, embedded in 3D matrices or in more complex assemblies of multiple cell types that mimic specific topologies of the tumour microenvironment. Such imaging and reconstitution approaches have provided us with a wealth of information on the motile behaviour and physical associations between macrophages and carcinoma cells and the role of the tumour microenvironment in influencing the movement of these cells. Finally, high-resolution imaging techniques have permitted researchers to correlate motility patterns with specific gene signatures and biochemical pathways in cells, pointing to potential targets for intervention. Here, we review experimental approaches employed in the study of macrophage interactions with carcinoma cells with an emphasis on imaging invasive and metastatic cell motility in breast carcinomas.