Effect of asymptomatic natural infections due to common mouse pathogens on the metastatic progression of B16 murine melanoma in C57BL/6 mice

To investigate whether the presence of infections in C57BL/6 mice influences the metastatic ability of B16 melanoma (B16M) cells, we compared the susceptibility to metastasis development of pathogen-free mice with that of mice from a colony endemically infected with several mouse pathogens. We found...

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Published in:Clinical & experimental metastasis 2005-11, Vol.22 (7), p.549-558
Main Authors: Rodríguez-Cuesta, Juan, Vidal-Vanaclocha, Fernando, Mendoza, Lorea, Valcárcel, María, Gallot, Natalia, Martínez de Tejada, Guillermo
Format: Article
Language:English
Subjects:
Animals
Bacterial Infections - classification
Bacterial Infections - epidemiology
Cell Culture Techniques
Disease Models, Animal
Disease Progression
Infections - epidemiology
Male
Melanoma, Experimental - complications
Melanoma, Experimental - pathology
Mice
Mice, Inbred C57BL
Murine hepatitis virus
Mycoplasma pulmonis
Neoplasm Metastasis
Parasitic Diseases - classification
Parasitic Diseases - epidemiology
Virus Diseases - classification
Virus Diseases - epidemiology
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Summary:To investigate whether the presence of infections in C57BL/6 mice influences the metastatic ability of B16 melanoma (B16M) cells, we compared the susceptibility to metastasis development of pathogen-free mice with that of mice from a colony endemically infected with several mouse pathogens. We found that, compared to seronegative controls, mice that were seropositive at least to Mouse Hepatitis Virus (MHV) and Mycoplasma pulmonis: (i) exhibited a higher interindividual variability in all the parameters quantifying metastatic progression; (ii) had elevated serum levels of proinflammatory cytokines both before and at the end of the experiment; (iii) were more susceptible to hepatic metastasis. Interestingly, final levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-18 correlated with the extent of hepatic colonization by the melanoma cells. To confirm the metastasis-enhancing effect of MHV and M. pulmonis we measured the ability of B16M cells to metastasize in pathogen-free animals housed for increasing time-intervals in the vicinity of MHV(+) animals. Notably, susceptibility to metastasis was lower in animals seronegative to MHV than in MHV(+) mice, whereas the latter were less susceptible to metastasis than MHV(+) M. pulmonis(+) mice. Seropositive animals had increased levels of TNF-alpha and IL-18 suggesting that MHV and M. pulmonis enhance the metastatic ability of melanoma cells by inducing the release of proinflammatory cytokines. While our results highlight the importance of using pathogen-free animals in metastasis studies, they emphasize the need for a comprehensive health monitoring of the mice used in such studies, particularly in case of using facilities lacking appropriate containment measures.
ISSN:0262-0898
1573-7276
DOI:10.1007/s10585-005-5261-9