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 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.
Departamento de Microbiología y Parasitología, Universidad de Navarra, Pamplona, Spain.
Juan
J
Rodríguez-Cuesta
Fernando
F
Vidal-Vanaclocha
Lorea
L
Mendoza
María
M
Valcárcel
Natalia
N
Gallot
Guillermo
G
Martínez de Tejada
D000818:Animals; D001424:Bacterial Infections / Q000145:classification / Q000453:epidemiology; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D018450:Disease Progression; D007239:Infections / Q000453:epidemiology*; D008297:Male; D008546:Melanoma, Experimental / Q000150:complications* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D010272:Parasitic Diseases / Q000145:classification / Q000453:epidemiology; D014777:Virus Diseases / Q000145:classification / Q000453:epidemiology