title: Development of a murine model of lymph node metastases suitable for immunotoxicity studies.
abstract: BACKGROUND
  Immunosuppressive drugs are associated with an increased risk of infections and in some cases neoplasia, particularly non-melanoma skin cancers. This paper describes the development of a model to test the effects of immunosuppressive drugs on local invasion and metastases of a squamous cell carcinoma in syngeneic, immunocompetent mice.
  
  
  METHODS
  SCC VII cells were labeled with 655 quantum dots (QDs), injected intramuscularly into C3H HEN mice and traffic and progressive growth in the draining popliteal lymph node were evaluated.
  
  
  RESULTS
  SCC VII cells express RAE-1, an NKG2D ligand, and were sensitive to natural killer (NK) cells in vitro. QDs were stable in SCC VII cells and showed no evidence of toxicity to the cells. In vivo, confocal microscopy showed that QD-labeled SCC VII cells could migrate to the draining node and microfluorimetry showed progressive traffic of QDs to the node. There was no evidence of systemic toxicity of QDs. Primary immunosuppression in SCID and SCID-beige mice and treatment of normal mice with immunosuppressive agents (anti-asialoGM1 and cyclophosphamide) can enhance traffic of QDs and/or metastases to the draining lymph node. In contrast, cyclosporine had no effect on traffic or metastases.
  
  
  CONCLUSIONS
  This model of local invasion and metastases may be useful in immunotoxicology for identifying and characterizing the hazard posed by selective immunosuppressive drugs.
authors.affiliation: Biologics Toxicology, Centocor R&D Inc., 145 King of Prussia Road, Radnor, PA 19087, USA. degenolf@its.jnj.com
authors.forename: Devon D
authors.initials: DD
authors.lastname: Egenolf
authors.forename: Patricia
authors.initials: P
authors.lastname: Rafferty
authors.forename: Kerry
authors.initials: K
authors.lastname: Brosnan
authors.forename: Mindi
authors.initials: M
authors.lastname: Walker
authors.forename: Jarrat
authors.initials: J
authors.lastname: Jordan
authors.forename: Dorie
authors.initials: D
authors.lastname: Makropoulos
authors.forename: Karl
authors.initials: K
authors.lastname: Kavalkovich
authors.forename: Sharon
authors.initials: S
authors.lastname: Watson
authors.forename: Laura
authors.initials: L
authors.lastname: Johns
authors.forename: Amy
authors.initials: A
authors.lastname: Volk
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bugelski
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000556:secondary*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008207:Lymphatic Metastasis; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000556:secondary*
chemical_list: D007166:Immunosuppressive Agents