title: NOD-scidIl2rg (tm1Wjl) and NOD-Rag1 (null) Il2rg (tm1Wjl) : a model for stromal cell-tumor cell interaction for human colon cancer.
abstract: OBJECTIVE
  Stromal cells and the extracellular environment are vital to human tumors, influencing growth and response to therapy. Human tumor cell lines lack stroma and transplantation into immunodeficient mice does not allow meaningful analyses of the effects of stroma on tumor cell growth. Studies of xenografts of primary human tumor fragments in nude mice and in early scid mouse models were constrained by poor tumor growth accompanied by host-versus-graft reactivity, dramatically altering tumor architecture and tumor microenvironment. In contrast, severely immunodeficient NOD-scid and NOD-Rag1 (null) strains carrying the IL2rg (null) mutation (NSG and NRG) support the growth of many types of human primary tumors.
  
  
  RESULTS
  We compared the take rate, growth and architectural preservation of 10 clinically distinct primary human colon cancers in NOD-scid, NOD-Rag1 (null) , NSG and NRG mice and determined the contribution of mouse and human cells to the stroma during tumor proliferation and expansion in secondary hosts and tumor response to treatment with 5-fluorouracil (5-FU). NSG and NRG mice more readily support growth of human primary colon tumor fragments than do NOD-scid, NOD-Rag1 (null) mice and maintain tumor architectural integrity in the primary recipient and through subsequent transplant generations. The human colon tumors were responsive to treatment with 5-FU. Human stromal cells in the primary graft were replaced by mouse-derived fibroblasts in a dynamic process during subsequent passages.
  
  
  CONCLUSIONS
  Human colon cancer xenografts propagated in NSG and NRG mice maintain structural fidelity while replacing human stromal cells with murine stromal cells.
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, UMass Memorial Health Care System, Worcester, MA, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Maykel
authors.forename: Jian Hua
authors.initials: JH
authors.lastname: Liu
authors.forename: Hanchen
authors.initials: H
authors.lastname: Li
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.forename: JeanMarie
authors.initials: J
authors.lastname: Houghton
mesh_terms: D000368:Aged; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D013047:Specific Pathogen-Free Organisms; D017154:Stromal Cells / Q000502:physiology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D018398:Homeodomain Proteins; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C064658:RAG-1 protein; D005472:Fluorouracil