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Tumours induced by Moloney murine sarcoma virus are clonal in rats, not clonal in mice
E D'Andrea1, L Tessarollo, C Menin
1Institute of Oncology, Interuniversity Center for Cancer Research (C.I.R.C.), University of Padova, Italy.
Abstract:
Moloney murine sarcoma virus (M-MSV) induces rapidly growing tumours in adult mice of most conventional strains. Rats are less susceptible to M-MSV oncogenesis, but the few rhabdomyosarcomas that do develop after viral inoculation of newborn animals closely resemble conventional malignancies: they develop after a long latency, grow progressively, and metastasize to regional lymph nodes and lungs. Southern blot analysis with a v-mos-specific probe of M-MSV-induced tumours in both species demonstrated an oligo-, monoclonal pattern of exogenous v-mos integration only in the rat system, while mouse tumours were not clonal in origin. Furthermore, the same type of analysis of lymph node and lung metastases showed that cell clones already present in the primary rat lesion colonized secondary sites during tumour progression. Apparently, Moloney murine leukemia virus (M-MuLV) was not involved in rhabdomyosarcoma pathogenesis since M-MuLV-specific DNA sequences could not be demonstrated in three of the six rat tumours. Finally, in all mouse tumours, unintegrated linear M-MSV proviruses could be readily detected.
Insights
Moloney murine sarcoma virus (M-MSV) causes tumors in mice and rats. Rat tumors show clonal v-mos integration and metastasis, unlike mouse tumors, suggesting different oncogenesis mechanisms.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Moloney murine sarcoma virus (M-MSV) is known to induce tumors in mice.
- Rats exhibit lower susceptibility to M-MSV oncogenesis, with developing rhabdomyosarcomas showing distinct characteristics.
- Understanding the molecular mechanisms of M-MSV-induced tumors across species is crucial for cancer research.
Purpose of the Study:
- To investigate the oncogenic mechanisms of Moloney murine sarcoma virus (M-MSV) in rats compared to mice.
- To analyze the integration pattern of the viral oncogene (v-mos) in M-MSV-induced tumors in both species.
- To examine the clonal origin and metastatic behavior of rhabdomyosarcomas in rats.
Main Methods:
- Southern blot analysis using a v-mos-specific probe to detect viral DNA integration.
- Comparative analysis of M-MSV-induced tumors in mice and rats.
- Investigation of Moloney murine leukemia virus (M-MuLV) involvement through DNA sequence analysis.
Main Results:
- M-MSV-induced rat tumors exhibited oligo- or monoclonal patterns of exogenous v-mos integration, unlike non-clonal mouse tumors.
- Metastases in rats originated from clones present in the primary tumor, indicating clonal expansion during progression.
- Moloney murine leukemia virus (M-MuLV) was not implicated in the pathogenesis of most rat tumors studied.
- Unintegrated linear M-MSV proviruses were detected in all M-MSV-induced mouse tumors.
Conclusions:
- Exogenous v-mos integration and clonal expansion are key features of M-MSV-induced rhabdomyosarcoma progression in rats, differing from mouse tumor development.
- The distinct patterns of viral integration and tumor progression in rats suggest species-specific oncogenic pathways.
- These findings highlight the importance of viral integration patterns in understanding tumor development and metastasis.
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