Abstract
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.
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Abbreviations
- B16M:
-
B16 melanoma
- ELISA:
-
enzyme-linked immunosorbent assay
- IL-18:
-
interleukin-18
- i.p.:
-
intraperitoneal
- LPS:
-
lipopolysaccharide
- MHV:
-
Mouse Hepatitis Virus
- TNF-α:
-
tumor necrosis factor α
References
W Nicklas FR Homberger B Illgen-Wilcke et al. (1999) ArticleTitleImplications of infectious agents on results of animal experiments. Report of the Working Group on Hygiene of the Society for Laboratory Animal Science (SOLAS) Lab Anim 33 IssueIDSuppl.1 S1:S39–87
DG Baker (1998) ArticleTitleFuture directions in rodent pathogen control Ilar J 39 IssueID4 312–15 Occurrence Handle11528091
G Lussier (1988) ArticleTitlePotential detrimental effects of rodent viral infections on long-term experiments Vet Res Commun 12 IssueID2–3 199–217 Occurrence Handle1:STN:280:BiaD2crmt1A%3D Occurrence Handle2847406
O Einarsson GP Geba Z Zhu et al. (1996) ArticleTitleInterleukin-11: Stimulation in vivo and in vitro by respiratory viruses and induction of airways hyperresponsiveness J Clin Invest 97 IssueID4 915–24 Occurrence Handle1:CAS:528:DyaK28XhvVaju7k%3D Occurrence Handle8613544
Howard (2002) ArticleTitleControl of variability Ilar J 43 IssueID4 194–201 Occurrence Handle1:CAS:528:DC%2BD38XntF2qu7g%3D Occurrence Handle12391394
L Zenner JP Regnault (2000) ArticleTitleTen-year long monitoring of laboratory mouse and rat colonies in French facilities: A retrospective study Lab Anim 34 IssueID1 76–83 Occurrence Handle1:STN:280:DC%2BD3c3itFWhtg%3D%3D Occurrence Handle10759370
DG Baker (1998) ArticleTitleNatural pathogens of laboratory mice, rats, and rabbits and their effects on research Clin Microbiol Rev 11 IssueID2 231–66 Occurrence Handle1:CAS:528:DyaK1cXislersrc%3D Occurrence Handle9564563
AK Hansen (2000) ArticleTitleNew infections to be considered in health monitoring of laboratory rodents Scand J Lab Anim Sci 27 IssueID2 65–83
SH Weisbroth R Peters LK Riley et al. (1998) ArticleTitleMicrobiological assessment of laboratory rats and mice Ilar J 39 IssueID4 272–90 Occurrence Handle11528088
W Nicklas P Baneux R Boot et al. (2002) ArticleTitleRecommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units Lab Anim 36 IssueID1 20–42 Occurrence Handle10.1258/0023677021911740 Occurrence Handle1:CAS:528:DC%2BD38XitFyqsb8%3D Occurrence Handle11831737
InstitutionalAuthorNameNational Research Council (1991) Infections Diseases of Mice and Rats: A Report of the Institute of Laboratory Animal Resources Committee on Infectious Diseases of Mice and Rats National Academy Press Washington, DC
F Vidal-Vanaclocha C Amezaga A Asumendi et al. (1994) ArticleTitleInterleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastases Cancer Res 54 IssueID10 2667–72 Occurrence Handle1:CAS:528:DyaK2cXjt1Wiur4%3D Occurrence Handle8168095
F Vidal-Vanaclocha A Alvarez A Asumendi et al. (1996) ArticleTitleInterleukin 1 (IL-1)-dependent melanoma hepatic metastasis in vivo; increased endothelial adherence by IL-1-induced mannose receptors and growth factor production in vitro J Natl Cancer Inst 88 IssueID3–4 198–205 Occurrence Handle1:CAS:528:DyaK28Xhslylt7c%3D Occurrence Handle8632494
F Vidal-Vanaclocha G Fantuzzi L Mendoza et al. (2000) ArticleTitleIL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1 Proc Natl Acad Sci USA 97 IssueID2 734–9 Occurrence Handle10.1073/pnas.97.2.734 Occurrence Handle1:CAS:528:DC%2BD3cXot1agsQ%3D%3D Occurrence Handle10639148
MT Carrascal L Mendoza M Valcarcel et al. (2003) ArticleTitleInterleukin-18 binding protein reduces B16 melanoma hepatic metastasis by neutralizing adhesiveness and growth factors of sinusoidal endothelium Cancer Res 63 IssueID2 491–7 Occurrence Handle1:CAS:528:DC%2BD3sXnt1Oisg%3D%3D Occurrence Handle12543807
SA Stohlman Q Yao CC Bergmann et al. (1995) Transcription and translation of proinflammatory cytokines following JHMV infection PJ Talbot (Eds) Corona and Related Viruses Plenum Press New York 173–8
SA Stohlman DR Hinton D Cua et al. (1995) ArticleTitleTumor necrosis factor expression during mouse hepatitis virus-induced demyelinating encephalomyelitis J Virol 69 IssueID9 5898–903 Occurrence Handle1:CAS:528:DyaK2MXns1Khsb4%3D Occurrence Handle7637037
Q Ning D Brown J Parodo et al. (1998) ArticleTitleRibavirin inhibits viral-induced macrophage production of TNF, IL-1, the procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response Am Assoc Immunol 65 3487–93
FR Homberger (1997) ArticleTitleEnterotropic mouse hepatitis virus Lab Anim 31 IssueID2 97–115 Occurrence Handle1:STN:280:ByiA3Mfgt1A%3D Occurrence Handle9175007
FR Homberger L Zhang SW Barthold (1998) ArticleTitlePrevalence of enterotropic and polytropic mouse hepatitis virus in enzootically infected mouse colonies Lab Anim Sci 48 IssueID1 50–54 Occurrence Handle1:STN:280:DyaK1c7nslSluw%3D%3D Occurrence Handle9517890
WC Lai M Bennett SP Pakes et al. (1990) ArticleTitleResistance to Mycoplasma pulmonis mediated by activated natural killer cells J Infect Dis 161 IssueID6 1269–75 Occurrence Handle1:STN:280:By%2BB28vnsFU%3D Occurrence Handle2140583
AL Smith SW Barthold MS Souza Particlede et al. (1991) ArticleTitleThe role of gamma interferon in infection of susceptible mice with murine coronavirus, MHV-JHM Arch Virol 121 IssueID1–4 89–100 Occurrence Handle1:CAS:528:DyaK38XhtVCjur8%3D Occurrence Handle1662041
SC Cartner JW Simecka JR Lindsey et al. (1995) ArticleTitleChronic respiratory mycoplasmosis in C3H/HeN and C57BL/6N mice: Lesion severity and antibody response Infect Immun 63 IssueID10 4138–42 Occurrence Handle1:CAS:528:DyaK2MXotlaht7o%3D Occurrence Handle7558330
MF Festing (2002) ArticleTitleThe design and statistical analysis of animal experiments Ilar J 43 IssueID4 191–3 Occurrence Handle1:CAS:528:DC%2BD38XntF2qu7s%3D Occurrence Handle12391393
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Rodríguez-Cuesta, J., Vidal-Vanaclocha, F., Mendoza, L. et al. Effect of Asymptomatic Natural Infections due to Common Mouse Pathogens on the Metastatic Progression of B16 Murine Melanoma in C57BL/6 Mice. Clin Exp Metastasis 22, 549–558 (2005). https://doi.org/10.1007/s10585-005-5261-9
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DOI: https://doi.org/10.1007/s10585-005-5261-9