Immunodeficient mouse strains display marked variability in growth of human melanoma lung metastases

Clin Cancer Res. 2009 May 15;15(10):3277-86. doi: 10.1158/1078-0432.CCR-08-2502. Epub 2009 May 15.


Purpose: Immunodeficient mice serve as critical hosts for transplantation of xenogeneic cells for in vivo analysis of various biological processes. Because investigators typically select one or two immunodeficient mouse strains as recipients, no comprehensive study has been published documenting differences in human tumor engraftment. Taking advantage of the increased metastatic potential of RhoC-expressing human (A375) melanoma cells, we evaluate four immunodeficient mouse strains: severe combined immunodeficiency (scid), nonobese diabetic (NOD)-scid, NOD-scid beta2m(null), and NOD-scid IL2Rgamma(null) as xenograft tumor recipients.

Experimental design: Bioluminescence, magnetic resonance imaging, and histopathology were used to monitor serial tumor growth. Natural killer (NK) cell function was examined in each mouse strain using standard (51)Chromium release assays.

Results: Melanoma metastases growth is delayed and variable in scid and NOD-scid mice. In contrast, NOD-scid beta2m(null) and NOD-scid IL2Rgamma(null) mice show rapid tumor engraftment, although tumor growth is variable in NOD-scid beta2m(null) mice. NK cells were detected in all strains except NOD-scid IL2Rgamma(null), and in vitro activated scid, NOD-scid, and NOD-scid beta2m(null) NK cells kill human melanoma lines and primary melanoma cells. Expression of human NKG2D ligands MHC class I chain-related A and B molecules renders melanoma susceptible to murine NK cell-mediated cytotoxicity and killing is inhibited by antibody blockade of murine NKG2D.

Conclusions: Murine NKG2D recognition of MICA/B is an important receptor-ligand interaction used by NK cells in immunodeficient strains to limit engraftment of human tumors. The absolute NK deficiency in NOD-scid IL2Rgamma(null) animals makes this strain an excellent recipient of melanoma and potentially other human malignancies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic / immunology
  • Flow Cytometry
  • GPI-Linked Proteins
  • Graft Survival
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin Receptor Common gamma Subunit / genetics
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology*
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Time Factors
  • Transplantation, Heterologous
  • Tumor Burden*
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism
  • rhoC GTP-Binding Protein


  • GPI-Linked Proteins
  • Histocompatibility Antigens Class I
  • Il2rg protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Interleukin Receptor Common gamma Subunit
  • MHC class I-related chain A
  • MICB antigen
  • Recombinant Fusion Proteins
  • ULBP2 protein, human
  • Luciferases
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoC GTP-Binding Protein