title: An in vivo mouse model of metastatic human thyroid cancer.
abstract: BACKGROUND
  Mouse models of metastatic human cancers are important tools in preclinical studies for testing new systematic therapies and studying effectors of cancer metastasis. The major drawbacks of current mouse models for metastatic thyroid cancer are that they have low metastasis rates and do not allow in vivo tumor detection. Here, we report and characterize an in vivo detectable metastasis mouse model of human thyroid cancer using multiple thyroid cancer cell lines.
  
  
  METHODS
  Human anaplastic thyroid cancer cell lines 8505C, C-643, SW-1736, and THJ-16T; follicular thyroid cancer cell lines FTC-133, FTC-236, and FTC-238; and Hürthle cell carcinoma cell line XTC-1 were transfected with a linearized pGL4.51[luc2/CMV/Neo] vector or transduced with lentivirus containing Luc2-eGFP reporter genes. The stably transfected cells were injected intravenously into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Tumors were detected with an in vivo imaging system-Xenogen IVIS. Vemurafenib, a BRAF inhibitor, was used to treat lung metastases generated from 8505C-Luc2 cells with a BRAF(V600E) mutation to test the accuracy of the model to evaluate response to therapy.
  
  
  RESULTS
  Intravenous injection of as few as 30,000 8505C-Luc2 cells produced lung metastases in 100% of the injected mice, and many of these mice also developed bone metastases at a later stage of the disease. Similarly, metastatic tumors also developed in all mice injected with C-643-Luc2, THJ-16T-Luc2, FTC-133-Luc2, FTC-236-Luc2, FTC-238-Luc2, and XTC-1-Luc2 cells. The metastases were easily detectable in vivo, and tumor progression could be dynamically and accurately followed and correlated with the actual tumor burden. Furthermore, disease progression could be easily controlled by adjusting the number of injected cells. The in vivo treatment of 8505C xenograft lung metastases with vemurafenib dramatically reduced the growth and signal intensity with good correlation with actual tumor burden.
  
  
  CONCLUSIONS
  Herein we report an in vivo detectable mouse model of metastatic human thyroid cancer that is reliable and reproducible. It will serve as a useful tool in the preclinical testing of alternative systematic therapies for metastatic thyroid cancer, and for functional studies of thyroid cancer tumor biology in vivo.
authors.affiliation: 1 Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute , National Institutes of Health, Bethesda, Maryland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.forename: Kelli
authors.initials: K
authors.lastname: Gaskins
authors.forename: Zhiya
authors.initials: Z
authors.lastname: Yu
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiong
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000473:pathology* / Q000556:secondary*; D018249:Adenoma, Oxyphilic / Q000473:pathology* / Q000556:secondary*; D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D013449:Sulfonamides / Q000627:therapeutic use; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib