Historical perspective of cell-cell fusion in cancer initiation and progression

This review discusses the topic of cell-cell fusion as it related to cancer causation, progression and metastasis. The relevant time period is over a century of research and analysis from the observation and hypothesis of Theodor Boveri in circa 1902 to the most recent publications in 2012. There are three main intertwined thrusts in this history: (i) progress in our overall understanding of cancer and the relative importance of mutations and aneuploidy; (ii) evidence that cell-cell fusion occurs and leads to aneuploidy in somatic cells, especially that cell-cell fusion allows rapid evolution of cancer cells that, most importantly, acquire a repertoire of traits from bone marrow-derived cells that facilitate metastasis; and (iii) evidence that viruses catalyze cell-cell fusion and that aneuploidy evolving from the hybrid cells is an important if not the principal basis for the association of viruses with certain cancers. There have been many competing hypotheses concerning all aspects of cancer development during this time period. Overall, the cell-cell fusion hypothesis has never gained preeminence. As a result, it has gone through long periods of obscurity only to be re-discovered because new supportive data appeared. Technical advances (especially in our ability to sequence genomes and establish the evolution of cell clones through cytogenetics) have recently made tools available that could help elucidate the role of cell-cell fusion, aneuploidy and viruses in cancer. Evidence seems to be increasing in support of the ideas stated by Boveri a century ago.