Giant Macrophages: Characteristics and Clinical Relevance

Tumor cell dissemination is mediated by a subpopulation of cells referred to as circulating tumor cells (CTCs), which have epithelial to mesenchymal properties and an inherent capacity to intravasate from the primary tumor, extravasate into secondary organs, and survive both in circulation and within the secondary organ. These properties have long been assumed to be cell autonomous; however, it is now clear that CTCs require the aid of secondary cells, such as macrophages. The role of tumor-associated macrophages (TAMs) as direct and indirect players in tumor cell dissemination will be discussed in this chapter. Special emphasis will be placed on the interplay between CTC and macrophages, focusing on the pro-tumorigenic function of TAMs at the level of secreted proteins, how TAMs enhance the invasive nature of tumor cells, the role of TAMs in promoting inflammation and a pro-tumor immune response, and the important role TAMs play in metastasis. Macrophages as therapeutic targets will also be discussed. Finally, the concept that macrophages can physically interact with CTCs or fuse with tumor cells to create giant macrophages or cell fusions that are invisible to the immune system and have enhanced migratory and metastatic capacities will be presented and detailed.