title: In-vivo fusion of human cancer and hamster stromal cells permanently transduces and transcribes human DNA.
abstract: After demonstrating, with karyotyping, polymerase chain reaction (PCR) and fluorescence in-situ hybridization, the retention of certain human chromosomes and genes following the spontaneous fusion of human tumor and hamster cells in-vivo, it was postulated that cell fusion causes the horizontal transmission of malignancy and donor genes. Here, we analyzed gene expression profiles of 3 different hybrid tumors first generated in the hamster cheek pouch after human tumor grafting, and then propagated in hamsters and in cell cultures for years: two Hodgkin lymphomas (GW-532, GW-584) and a glioblastoma multiforme (GB-749). Based on the criteria of MAS 5.0 detection P-values ≤0.065 and at least a 2-fold greater signal expression value than a hamster melanoma control, we identified 3,759 probe sets (ranging from 1,040 to 1,303 in each transplant) from formalin-fixed, paraffin-embedded sections of the 3 hybrid tumors, which unambiguously mapped to 3,107 unique Entrez Gene IDs, representative of all human chromosomes; however, by karyology, one of the hybrid tumors (GB-749) had a total of 15 human chromosomes in its cells. Among the genes mapped, 39 probe sets, representing 33 unique Entrez Gene IDs, complied with the detection criteria in all hybrid tumor samples. Five of these 33 genes encode transcription factors that are known to regulate cell growth and differentiation; five encode cell adhesion- and transmigration-associated proteins that participate in oncogenesis and/or metastasis and invasion; and additional genes encode proteins involved in signaling pathways, regulation of apoptosis, DNA repair, and multidrug resistance. These findings were corroborated by PCR and reverse transcription PCR, showing the presence of human alphoid (α)-satellite DNA and the F11R transcripts in additional tumor transplant generations. We posit that in-vivo fusion discloses genes implicated in tumor progression, and gene families coding for the organoid phenotype. Thus, cancer cells can transduce adjacent stromal cells, with the resulting progeny having permanently transcribed genes with malignant and other gene functions of the donor DNA. Using heterospecific in-vivo cell fusion, genes encoding oncogenic and organogenic traits may be identified.
authors.affiliation: Garden State Cancer Center, Center for Molecular Medicine and Immunology, Morris Plains, New Jersey, United States of America; Immunomedics, Inc., Morris Plains, New Jersey, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.affiliation: Genome Explorations, Inc., Memphis, Tennessee, United States of America.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Rooney
authors.affiliation: Immunomedics, Inc., Morris Plains, New Jersey, United States of America.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Loo
authors.affiliation: Immunomedics, Inc., Morris Plains, New Jersey, United States of America.
authors.forename: Donglin
authors.initials: D
authors.lastname: Liu
authors.affiliation: Immunomedics, Inc., Morris Plains, New Jersey, United States of America.
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Chang
mesh_terms: D000818:Animals; D002459:Cell Fusion; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D006224:Cricetinae; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D017154:Stromal Cells; D014158:Transcription, Genetic; D014161:Transduction, Genetic