Establishment of a lymph node metastasis model from subcutaneous tumors of gastrointestinal stromal tumor model cells

Oncol Rep. 2009 Feb;21(2):407-11.

Abstract

There is currently no suitable animal model of metastasis using cultured human gastrointestinal stromal tumor cells even though the molecular mechanisms of c-KIT-mediated progression and metastasis should be clarified. Ba/F3 murine lymphocyte cells transduced with mutant c-KIT have been utilized to analyze some molecular mechanisms related to a constitutively activated c-KIT signaling and to assess the efficacy of molecular-targeted inhibitors. Using this cellular system, we coincidentally discovered the development of axillary and inguinal lymph node swelling three weeks after subcutaneous injection of Ba/F3 cells with c-KIT mutation into nude mice. Mutation-specific PCR detected c-KIT mutation in the swollen lymph nodes but not in unmetastasized normal lymph nodes, indicating that the lymph nodes contain tumor cells which should come from a primary subcutaneous tumor. Microscopic observation revealed tumor cells infiltrating through lymphatic follicles with Ki-67-positive staining to distinguish them from lymphocytes. The significance of this model is helpful to understand the molecular mechanisms of c-KIT-mediated metastasis and is useful for assessments of molecular therapeutics and in vivo imaging.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Female
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / pathology*
  • Immunohistochemistry
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology*
  • Mice
  • Mutation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Soft Tissue Neoplasms / pathology
  • Stem Cell Factor / genetics*
  • Xenograft Model Antitumor Assays

Substances

  • Stem Cell Factor