title: New metastatic model of human small-cell lung cancer by orthotopic transplantation in mice.
abstract: Small-cell lung cancer (SCLC) is an aggressive cancer with high metastatic ability and novel strategies against the metastasis are urgently needed to improve SCLC treatment. However, the mechanism of metastasis of SCLC remains largely to be elucidated. For further studies of SCLC metastasis, we developed a new orthotopic transplantation model in mice. We established a GFP-labeled subline from the human SCLC cell line DMS273 and transplanted them orthotopically into the lung of nude mice with Matrigel. The GFP-labeled cells showed significant metastatic activity and formed metastatic foci in distant tissues such as bone, kidney, and brain, as observed in SCLC patients. From a bone metastasis focus of the mouse, we isolated another subline, termed G3H, with enhanced metastatic potential and higher hepatocyte growth factor (HGF) expression than the parental line. Further studies indicated that the HGF/MET signaling pathway was involved in in vitro motility and invasion activities of the G3H cells and treatments with MET inhibitors decreased formation of distant metastases in our orthotopic model using G3H cells. These data indicated that our model mimics the clinical aspect of SCLC such as metastatic tropism and autocrine of HGF/MET signaling. Compared with other orthotopic SCLC models, our model has a superior ability to form distant metastases. Therefore, our model will provide a valuable tool for the study of SCLC metastasis.
authors: Institute of Microbial Chemistry, Numazu, Japan.
authors: Shuichi
authors: S
authors: Sakamoto
authors: Hiroyuki
authors: H
authors: Inoue
authors: Shunichi
authors: S
authors: Ohba
authors: Yasuko
authors: Y
authors: Kohda
authors: Ihomi
authors: I
authors: Usami
authors: Tohru
authors: T
authors: Masuda
authors: Manabu
authors: M
authors: Kawada
authors: Akio
authors: A
authors: Nomoto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001859:Bone Neoplasms / Q000556:secondary; D001932:Brain Neoplasms / Q000556:secondary; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000556:secondary*; D013450:Sulfones / Q000494:pharmacology
chemical_list: C480541:5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-((2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-1,3-dihydro-2H-indol-2-one; D000970:Antineoplastic Agents; C066855:HGF protein, human; D007211:Indoles; D013450:Sulfones; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D002945:Cisplatin
keywords: Hepatocyte growth factor; MET; metastasis; orthotopic transplantation; small-cell lung cancer
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