Inception of the metastatic phenotype by macrophage-cancer cell fusion.
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It is now well-established that patient outcome are good if the primary tumor has not spread; can be surgically removed; treated locally with radiation; or preventive chemotherapy can be applied. In contrast, when cancer cells have disseminated, the mortality rates increase significantly and therapeutic treatment strategies are eventually switched from curative to palliative. Although responsible for the majority of cancer deaths, knowledge about the emergence of metastatic cells remains scarce. Nevertheless, in vivo evidence in animal models and humans is accumulating and supportive of the century-old macrophage-cancer cell fusion theory. The theory implies that the metastatic cells emerge from a fusion event and express the phenotypes of the migratory macrophage and the proliferative cancer cell. Although the theory is steadily gaining approval from cancer researchers, it still lacks essential attention from the broader research community. We will review the current knowledge surrounding the macrophage-cancer cell fusion theory. It is our believe that work on the fusion theory and in the research fields related to it will enhance our understanding of metastasis, and ultimately lead to the development of novel and effective strategies for the treatment of metastatic cancers.