Tumor cell-bone marrow cell fusion: a unifying explanation for metastasis Free

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Despite the vast amount of information on the nature of the cancer cell and its environment, the underlying causes of invasion and metastasis remain elusive. A unifying explanation is the fusion of cancer cells with migratory bone marrow-derived cells. Tumor cell-bone marrow cell hybrids have been identified in human and animal cancers where they were frequently associated with metastasis. Thus, the question is no longer whether, but rather to what extent does tumor cell fusion contribute to tumor progression? Such hybrids are aneuploid with aberrant karyotypes. They exhibit migratory phenotypes in vitro and high metastatic potential in vivo. Tumor cell hybrids are up-regulated for expression of metastasis-related genes such as cMet, SPARC, MCR1 and GnT-V. They express aberrant N-glycosylation patterns associated with poor survival in melanomas and carcinomas of the breast and colon. They have high levels of autophagy, a characteristic of aggressive cancers. Moreover, tumor-bone marrow hybrids could explain two paradigms of cancer progression--the origin of cancer stem cells and the phenomenon of epidermal-mesenchymal transition. Tumor-bone marrow hybrid phenotypes arise through co-expression of imprinted genomes from the parental cells of different developmental lineages. It is proposed that this is the underlying basis for gene expression patterns in cancer, that is, hybrid and tumor epigenomes might be two faces of the same phenomenon.