A Living Oncogenic Microcell Isolated from Mammalian Cancers
Lusi, E. A.; Claudia, R.; Caicci, F.
Show abstract
The biological mechanisms underlying oncogenesis are traditionally interpreted within the frameworks of somatic mutation, clonal evolution, and, in some cases, viral infection. Here, we report the isolation, purification and characterization of a distinct class of autonomous microcellular organisms consistently recovered from independent mammalian neoplastic tissues. These entities measure approximately 1-3 microns in diameter and exhibit a reproducible organic wall assembly with internal compartmentalization revealed by transmission and scanning electron microscopy. Biochemical and molecular analyses demonstrated a predominantly RNA-based genetic system associated with intrinsic reverse transcriptase activity. High-throughput sequencing revealed a highly distributed multipartite genetic repertoire comprising approximately 2.63 Mb organized across 1,597 independent RNA units. Canonical bacterial signatures, including 16S ribosomal RNA, were not detected, and the recovered architecture lacked the genomic organization characteristic of known retroviruses. Instead, multiple RNA units contained domains related to reverse transcriptase, mobile genetic elements, regulatory functions, and oncogene-associated sequences. Purified preparations containing intact microcells induced rapid cellular transformation in vitro and aggressive malignancies in murine models. In contrast, matched preparations filtered through a 0.2 micron membrane failed to exhibit reverse transcriptase activity, cellular transformation, or tumorigenicity, demonstrating that the observed biological effects reside within intact micron-scale particles rather than filterable viral agents or soluble components. Furthermore, vaccination targeting the microcellular organisms was associated with tumour regression and restoration of tissue architecture in dogs with naturally occurring cancers. Collectively, these findings describe a previously unrecognized autonomous microcell lineage within mammalian hosts possessing distinctive structural, genetic and biological properties. The combination of cellular organization, a highly distributed multipartite RNA repertoire, intrinsic reverse transcriptase activity, and oncogenic potential suggest a biological strategy not readily accommodated within current frameworks of cancer biology, virology or cellular evolution.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Prevalent Gut Phages Encode Modular Adhesins Mediating Epithelial Binding and Endoplasmic Reticulum Trafficking 94%
- Subcellular reorganization upon phage infection reveals stepwise assembly of viral particles from membrane-associated precursors 94%
- Integrative functional genomics decodes herpes simplex virus 1 94%
Similar papers in this journal
- Diversification of giant and large eukaryotic dsDNA viruses predated the origin of modern eukaryotes 94%
- Efficient packaging of HIV-1 genomes via recognition of its adenosine-rich content by a heterologous RNA-binding domain 94%
- Epstein-Barr virus reprograms human B-lymphocytes immediately in the pre-latent phase of infection 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.