Spontaneous Cell Fusion as the Mechanism of Cancer Progression and Metastasis

ABSTRACT: The mechanism of prostate cancer (PCa) progression and metastasis remains unclear. Spontaneous cancer cell fusion is one theory of etiology. This essay takes a reductionist approach to highlight spontaneous cancer cell fusion as the primary mechanism of PCa progression and metastasis. PCa cells can fuse with adjacent cancer cells or various bystander cells in the tumor microenvironment. The fate of the fusion hybrids is determined by the similarity of cell cycle timing between the fusing cancer cell and the cell being fused. A tumor cell with high proliferative activity, when fused with a non-proliferating neighbor, results in growth arrest. However, fusion with a proliferative cell may lead to abnormal hybrid cell division, causing the hybrid genome to undergo random recombination. This creates a hybrid derivative clone with a genotype and phenotype distinct from those of both the parental cancer cell and the cell being fused. The progression of tumor cell heterogeneity is dynamic, as the hybrid derivative clone can inherit the ability to fuse. Their fusion with various proliferative cells in the tumor microenvironment generates additional hybrid clones, each with a new genomic makeup and altered phenotype. The spontaneity of PCa cell fusogenicity enables an ever-changing tumor cell heterogeneity, which is the root cause of the pathological behavior of PCa progression and metastasis.