Cited by 550Phagocytosis and Immune RegulationCell death mechanisms and regulationCancer-related Molecular Pathways

Horizontal transfer of oncogenes by uptake of apoptotic bodies

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Bergsmedh, Anna, Szeles, Anna, Henriksson, Marie, Bratt, Anders, Folkman, M. Judah, Spetz, Anna-Lena, Holmgren, Lars·2001·Proceedings of the National Academy of Sciences

Abstract

Tumor formation involves the accumulation of a series of genetic alterations that are required for malignant growth. In most malignancies, genetic changes can be observed at the chromosomal level as losses or gains of whole or large portions of chromosomes . Here we provide evidence that tumor DNA may be horizontally transferred by the uptake of apoptotic bodies. Phagocytosis of apoptotic bodies derived from H-ras V12 - and human c-myc-transfected rat fibroblasts resulted in loss of contact inhibition in vitro and a tumorigenic phenotype in vivo . Fluorescence in situ hybridization analysis revealed the presence of rat chromosomes or of rat and mouse fusion chromosomes in the nuclei of the recipient murine cells. The transferred DNA was propagated, provided that the transferred DNA conferred a selective advantage to the cell and that the phagocytotic host cell was p53-negative. These results suggest that lateral transfer of DNA between eukaryotic cells may result in aneuploidy and the accumulation of genetic changes that are necessary for tumor formation.

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Authors
Bergsmedh, A., Szeles, A., Henriksson, M., Bratt, A., Folkman, M. J., Spetz, A.-L., & Holmgren, L.
Affiliations
  • Karolinska Institutet (SE)
  • Cancer Center Karolinska Hospital R8:03, SE 17176, Stockholm, Sweden; Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden; Surgical Research Laboratory, Children's Hospital, Boston, Ma 02115; Center for Infectious Diseases, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, S-141 86, Huddinge, Sweden
Venue
Proceedings of the National Academy of Sciences
Published
2001-05-15
Volume
98
Issue
11
Pages
6407-6411
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1991293757
Cited by
550
References
31
Citations by year
2026: 12 · 2025: 16 · 2024: 31 · 2023: 37 · 2022: 34 · 2021: 42 · 2020: 29 · 2019: 29 · 2018: 21 · 2017: 22 · 2016: 37 · 2015: 15 · 2014: 20 · 2013: 21 · 2012: 18
FWCI
5.93
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
horizontal gene transfer, apoptotic bodies, phagocytosis, oncogenes, H-Ras V12, c-Myc, tumor formation, contact inhibition, chromosome fusion, aneuploidy, tumor DNA
MeSH terms
Animals, Cell Transformation, Neoplastic, Cells, Cultured, DNA, Neoplasm, Fibroblasts, Humans, Genes, ras, Genes, myc, Mice, SCID, Apoptosis, Mice, Rats

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