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

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.