title: A murine xenograft model of spontaneous metastases of human lung adenocarcinoma.
abstract: BACKGROUND
  The flank is commonly used for primary xenografts in mice, but it is rare for these tumors to metastasize. Tail vein injection creates a pattern of metastases, but is artificial. We hypothesized that the liver is a convenient alternative xenograft site and that metastases would gradually proceed spontaneously.
  
  
  METHODS
  Using 15 NOD.CB17-Prkdc(scid)/NcrCrl (NOD/SCID) mice, 10,000 A549 cells were xenografted into the liver while a second group of five mice were xenografted in the flank with 100,000 A549 cells as a control. Mice were euthanized and grossly dissected at 7 wk. A third group of seven mice received liver xenografts with A549 and a mouse each week was euthanized for 7 wk and evaluated. The liver, lung, and spleen were examined histologically.
  
  
  RESULTS
  At 7 wk, 15/15 liver xenografted mice had gross primary tumor in the liver. Histologic review confirmed multiple microscopic foci of metastatic disease in all mice (15/15) throughout the lungs, mediastinal nodes, and spleen. The control group had primary tumor in the flank (4/5), but none had histologic evidence of metastases. Serially euthanized liver xenografted mice revealed evidence of a gradual spontaneous metastatic model system with the first histologic findings of micrometastases appearing in the lungs by wk 5, which became wide spread by wk 7. Splenic and mediastinal lymph node metastases developed in wk 6 and 7.
  
  
  CONCLUSIONS
  Liver xenografting of A549 cells into NOD/SCID mice is a reliable way of developing widespread micrometastases. This model allows the study of a gradually developing solid tumor with subsequent metastatic spread.
authors.affiliation: Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Harris
authors.forename: James
authors.initials: J
authors.lastname: Shin
authors.forename: Beverly
authors.initials: B
authors.lastname: Lee
authors.forename: Kristen
authors.initials: K
authors.lastname: Pelosky
authors.forename: Craig M
authors.initials: CM
authors.lastname: Hooker
authors.forename: Kirsten
authors.initials: K
authors.lastname: Harbom
authors.forename: Alicia
authors.initials: A
authors.lastname: Hulbert
authors.forename: Cynthia
authors.initials: C
authors.lastname: Zahnow
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Yang
authors.forename: Stephen
authors.initials: S
authors.lastname: Baylin
authors.forename: Cory
authors.initials: C
authors.lastname: Brayton
authors.forename: Malcolm V
authors.initials: MV
authors.lastname: Brock
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008175:Lung Neoplasms / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods; D013160:Splenic Neoplasms / Q000556:secondary; D014183:Transplantation, Heterologous