期刊
INTERNATIONAL JOURNAL OF CANCER
卷 131, 期 1, 页码 49-58出版社
WILEY
DOI: 10.1002/ijc.26327
关键词
cell fusion; cancer stroma; metastasis; gene transfer; glioblastoma
类别
资金
- American Cancer Society [IN-581]
- USPHS (National Institutes of Health) [CA12374]
- National Cancer Institute, NIH, Damon Runyon Memorial Fund for Cancer Research
- National Cancer Institute, NIH
- Damon Runyon Memorial Fund for Cancer Research
Cell fusion in vitro has been used to study cancer, gene mapping and regulation, and the production of antibodies via hybridomas. However, in-vivo heterosynkaryon formation by cellcell fusion has received less attention. This investigation describes the spontaneous fusion of a human glioblastoma with normal hamster cells after xenogeneic transplantation, resulting in malignant cells that express both human and hamster genes and gene products, and retention of glioblastoma traits with an enhanced ability to metastasize. Three of 7 human genes found showed translation of their proteins during serial propagation in vivo or in vitro for years; namely, CD74, CXCR4 and PLAGL2, each implicated with malignancy or glioblastoma. This supports the thesis that genetic hybridization of cancer and normal cells can transmit malignancy and also, as first described herein, regulatory genes involved in the tumor's organotypic morphology. Evidence also is increasing that even cell-free human cancer DNA can induce malignancy and transfer genetic information to normal cells. Hence, we posit that the transfer of genetic information between tumor and stromal cells, whether by cellcell fusion or other mechanisms, is implicated in the progression of malignancy, and may further define the crosstalk between cancer cells and their stromal neighbors.
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