Clinical & Experimental Metastasis

, Volume 22, Issue 7, pp 549–558 | Cite as

Effect of Asymptomatic Natural Infections due to Common Mouse Pathogens on the Metastatic Progression of B16 Murine Melanoma in C57BL/6 Mice

  • Juan Rodríguez-Cuesta
  • Fernando Vidal-Vanaclocha
  • Lorea Mendoza
  • María Valcárcel
  • Natalia Gallot
  • Guillermo Martínez de Tejada


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)-α 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-α 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.


B16 melanoma C57BL/6 mice liver metastasis MHV murine infections Mycoplasma pulmonis proinflammatory cytokines TNF-α experimental variability animal model 



B16 melanoma


enzyme-linked immunosorbent assay








Mouse Hepatitis Virus


tumor necrosis factor α


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Copyright information

© Springer 2006

Authors and Affiliations

  • Juan Rodríguez-Cuesta
    • 1
    • 4
  • Fernando Vidal-Vanaclocha
    • 2
    • 3
  • Lorea Mendoza
    • 3
  • María Valcárcel
    • 3
  • Natalia Gallot
    • 3
  • Guillermo Martínez de Tejada
    • 1
    • 5
  1. 1.Departamento de Microbiología y ParasitologíaUniversidad de NavarraPamplonaSpain
  2. 2.Department of Cellular Biology and HistologyBasque Country University School of Medicine and DentistryLeioaSpain
  3. 3.Pharmakine Ltd., Bizkaia Technology ParkDerioSpain
  4. 4.Centro de Investigación Cooperativa en Biociencias (CIC bioGUNE)Parque Tecnológico de BizkaiaDerioSpain
  5. 5.Departamento de Microbiología y ParasitologíaUniversidad de NavarraPamplonaSpain

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