Cell-cell fusion as a mechanism of DNA exchange in cancer.
Cell-cell fusion as a mechanism of DNA exchange in cancer.
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DOI：
10.18632/oncotarget.23715
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发表时间：
2018-01-19
期刊：
影响因子：
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通讯作者：
Bui JD
中科院分区：
文献类型：
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作者：
Searles SC;Santosa EK;Bui JD
细胞-细胞融合描述了两个细胞将其质膜结合并成为单个细胞的过程，该过程拥有并保留来自每个亲代细胞的某些遗传信息。在这里，我们使用最初开发用于研究细胞外囊泡靶向的基于 Cre-loxP 的方法，发现癌细胞通过细胞-细胞融合事件在体外自发且快速地将 DNA 递送至非癌细胞。所得杂交细胞是非整倍体，与非杂交癌细胞相比，具有增强的克隆多样性和化疗耐药性。我们还观察到体内黑色素瘤细胞与造血和非造血谱系的非癌细胞之间发生细胞-细胞融合。这些发现表明细胞与细胞融合发生在癌症的自然进展过程中，并表明这种机制有可能导致癌症中观察到的大规模基因组改变。此外，这些发现在某种程度上与最近的出版物相矛盾，最近的出版物表明 Cre-loxP 方法仅测量细胞外囊泡介导的细胞间通讯。
Cell-cell fusion describes the process by which two cells combine their plasma membranes and become a single cell, possessing and retaining certain genetic information from each parent cell. Here, using a Cre-loxP-based method initially developed to investigate extracellular vesicle targeting, we found that cancer cells spontaneously and rapidly deliver DNA to non-cancer cells in vitro via a cell-cell fusion event. The resulting hybrid cells were aneuploid and possessed enhanced clonal diversity and chemoresistance compared to non-hybrid cancer cells. We also observed cell-cell fusion to occur in vivo between melanoma cells and non-cancer cells of both hematopoietic and non-hematopoietic lineages. These findings suggest that cell-cell fusion occurs during the natural progression of cancer and show that this mechanism has the potential to cause massive genomic alterations that are observed in cancer. Furthermore, these findings somewhat contradict recent publications suggesting that the Cre-loxP method measures only extracellular vesicle-mediated intercellular communication.