title: Surgically-Induced Multi-organ Metastasis in an Orthotopic Syngeneic Imageable Model of 4T1 Murine Breast Cancer.
abstract: OBJECTIVE
  Murine models of breast cancer with a metastatic pattern similar to clinical breast cancer in humans would be useful for drug discovery and mechanistic studies. The 4T1 mouse breast cancer cell line was developed by Miller et al. in the early 1980s to study tumor metastatic heterogeneity. The aim of the present study was to develop a multi-organ-metastasis imageable model of 4T1.
  
  
  METHODS
  A stable 4T1 clone highly-expressing red fluorescent protein (RFP) was injected orthotopically into the right second mammary fat pad of BALB/c mice. The primary tumor was resected on day 18 after tumor implantation, when the average tumor volume reached approximately 500-600 mm(3).
  
  
  RESULTS
  When the post-surgical mice were sacrificed 6-8 weeks after cell implantation, metastases were found in the lung in 91%; in the lymph nodes in 100%, including axillary nodes; in the brain in 25%; and in bone in 42% of the mice. The metastases were readily visualized by fluorescence imaging. Detailed fluorescence analysis visualized extensive metastasis in the thoracic cavity and the lymphatic system. Large metastatic nodules in the lung involved most of the pulmonary parenchyma in all lobes. In the liver, fluorescent macroscopic metastatic nodules were found under the capsule. Bone metastases were found mainly in the spine and thigh bone.
  
  
  CONCLUSIONS
  Metastasis appeared to be enhanced by resection of the primary tumor. The metastatic pattern in the model thus reflected the clinical metastatic pattern of breast cancer and should be of use for discovery and evaluation of novel therapeutics.
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A. Department of Surgery, University of California, San Diego, CA, U.S.A. all@anticancer.com.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: AntiCancer, Inc., San Diego, CA, U.S.A.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D005260:Female; D008164:Luminescent Proteins / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery*; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000473:pathology*; D009928:Organ Specificity; D000097573:Red Fluorescent Protein
chemical_list: D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein
keywords: Balb-c mice; Breast cancer; RFP; imaging; metastasis; orthotopic; syngeneic; tumor resection