Increased numbers of spontaneous SCLC metastasis in absence of NK cells after subcutaneous inoculation of different SCLC cell lines into pfp/rag2 double knock out mice

Cancer Lett. 2009 Sep 18;282(2):146-51. doi: 10.1016/j.canlet.2009.03.005. Epub 2009 Apr 5.


Spontaneous metastases in small cell lung cancer (SCLC) occur regularly in patients but seldom if any in conventional xenograft mouse models. To overcome this problem, SCLC cells were grafted subcutaneously onto pore forming protein and recombination activating gene 2 double knock out (pfp/rag2) mice and in severe combined immunodeficient (scid) mice. Primary tumours grew well in both mouse strains, while metastases occurred frequently in the pfp/rag2 mice and infrequently in scid mice. Hence NK cells, which are inactive in pfp/rag2 mice, play an important role in SCLC metastasis formation in xenograft models. This observation is in agreement with clinical studies, where a high NK cell number in the blood is correlated with a better prognosis of the patient.

MeSH terms

  • Animals
  • Carcinoma, Small Cell / pathology*
  • Cell Line, Tumor
  • DNA-Binding Proteins / physiology*
  • Humans
  • Immunohistochemistry
  • Killer Cells, Natural / physiology*
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Pore Forming Cytotoxic Proteins / physiology*
  • Transplantation, Heterologous


  • DNA-Binding Proteins
  • Pore Forming Cytotoxic Proteins
  • Rag2 protein, mouse