Abstract

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 β2mnull, and NOD-scid IL2Rγ;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 51Chromium release assays. Results: Melanoma metastases growth is delayed and variable in scid and NOD-scid mice. In contrast, NOD-scid β2mnull and NOD-scid IL2Rγ null mice show rapid tumor engraftment, although tumor growth is variable in NOD-scid β2mnull mice. NK cells were detected in all strains except NOD-scid IL2Rγnull, and in vitro activated scid, NOD-scid, and NOD-scid β2mnull NK cells kill human melanoma lines and primary melanoma cells. Expression of human NKG2D ligands MHC class I chain-related Aand 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 IL2Rγnull animals makes this strain an excellent recipient of melanoma and potentially other human malignancies. © 2009 American Association for Cancer Research.

Department(s)

Biological Sciences

Publication Status

Free Access

Comments

National Cancer Institute, Grant P30CA091842

International Standard Serial Number (ISSN)

1078-0432

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2025 American Association for Cancer Research, All rights reserved.

Publication Date

15 May 2009

PubMed ID

19447870

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