title: 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.
authors.affiliation: Department of Gastroenterological Surgery, Okayama University, Okayama 700-8558, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Sakurama
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naomoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ohara
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Munenori
authors.initials: M
authors.lastname: Takaoka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tomono
authors.forename: Toru
authors.initials: T
authors.lastname: Tanida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Noma
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanabe
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Takayuki
authors.initials: T
authors.lastname: Motoki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shirakawa
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yamatsuji
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taguchi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012983:Soft Tissue Neoplasms / Q000473:pathology; D019089:Stem Cell Factor / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D019089:Stem Cell Factor