Abstract
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.
Highlights
The impact of cell fusion on biology and genetics has been of a subject of interest for many years
Numerous observations in experimental animals and some human subjects suggest that fusion of one normal cell with another can induce malignant transformation, and fusion of a cancer cell with other cells can spark the progression of an existing to a more malignant phenotype (Figure 1A)
The hypothesis we explore is that events, such as fusion, that induce or closely follow upon malignant transformation and progression of cancer could have been appropriated by evolution for defenses against cancer
Summary
The impact of cell fusion on biology and genetics has been of a subject of interest for many years (see [1,2] for review). Numerous observations in experimental animals and some human subjects suggest that fusion of one normal cell with another can induce malignant transformation, and fusion of a cancer cell with other cells can spark the progression of an existing to a more malignant phenotype (Figure 1A). (i) how often cell fusion cell occurs at the inception after development cancer; important questions concerning fusion in cancer haveor long persisted These of questions (ii) whether cell fusion causes or results from malignant transformation;. As we consider the existing set of clinical and experimental observations, it is evident that because fusion events cannot be witnessed, further investigation of human cancers and basic cell biology will offer only provisional answers to the questions posed above. As we discuss observations suggesting cell fusion could promote resistance to malignancy, we shall consider how specific blockade of cell fusion would modify such resistance
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