Cell Fusion in Malignancy: A Cause or Consequence? A Provocateur or Cure?

Cell fusion has been observed in malignancy, and cancer cells have been found especially apt to fuse with other cells. Investigation of human and experimental malignancies suggests spontaneous fusion of normal cells can induce manifold genetic changes and manifestations of malignant transformation. Fusion of transformed cells with other cells can promote the progression of cancer to more malignant forms. However, observations in various fields suggest cell fusion also potentially contributes to natural defenses against cancer. Thus, cell fusion potentially corrects genetic and/or phenotypic changes underlying malignant transformation. Cell fusion also might help nonmalignant cells in tumors thwart tumor growth. Perhaps most importantly, cell fusion may generate genetic changes that lead to the expression of neoantigens, provide the mass of neoantigen expression needed to elicit immunity, and promote the function of antigen-presenting cells in a way that favors protective immunity as a defense against malignancy. To the extent that cell fusion promotes cellular, tissue, and/or systemic resistance to malignancy, the propensity of tumor cells to fuse with other cells might constitute a natural defense against malignancy.