title: Horizontal transmission and retention of malignancy, as well as functional human genes, after spontaneous fusion of human glioblastoma and hamster host cells in vivo.
abstract: 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 cell-cell 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 cell-cell fusion or other mechanisms, is implicated in the progression of malignancy, and may further define the crosstalk between cancer cells and their stromal neighbors.
authors.affiliation: Garden State Cancer Center, Center for Molecular Medicine and Immunology, Morris Plains, NJ, USA. dmg.gscancer@att.net
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: David
authors.initials: D
authors.lastname: Zagzag
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Heselmeyer-Haddad
authors.forename: Lissa Y
authors.initials: LY
authors.lastname: Berroa Garcia
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: Meiyu
authors.initials: M
authors.lastname: Loo
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Chang
authors.forename: David V
authors.initials: DV
authors.lastname: Gold
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002678:Chimera; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells / Q000473:pathology*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; C527276:CXCR4 protein, human; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C114598:PLAGL2 protein, human; D016601:RNA-Binding Proteins; D019718:Receptors, CXCR4; D014157:Transcription Factors; C045084:invariant chain