Optically imageable metastatic model of human breast cancer.
We report an optically imageable orthotopic metastatic nude mouse model of the human breast cancer MDA-MB-435 expressing green fluorescent protein (GFP). We demonstrate fluorescent imaging of primary and metastatic growth in live tissue and in intact animals. Fragments of tumor tissue expressing GFP were sutured into the pocket in the right second mammary gland. Tumor tissue was strongly fluorescent, enabling whole-body imaging of tumor growth by week 5. Neovascularization of the primary tumor was also visualized by whole-body imaging by contrast of the vessels to the fluorescent tumor. At autopsy, the MDA-MB-435-GFP was found to have metastasized to various organs, including the lung in 55% of the animals, the lymph nodes in 15% of the animals including axillary nodes, and the liver in 10% of the animals. These metastases could be visualized in fresh tissue by fluorescent 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. Lymph node metastasis was found mainly in the axillary area. In the liver, fluorescent macroscopic metastatic nodules were found under the capsule. The metastatic pattern in the model thus reflected clinical metastatic breast cancer and provides a powerful model for drug discovery for this disease.
Li
Xiaoming
X
AntiCancer, Inc, San Diego, California 92111, USA.
Wang
Jinwei
J
An
Zili
Z
Yang
Meng
M
Baranov
Eugene
E
Jiang
Ping
P
Sun
Fangxian
F
Moossa
A R
AR
Hoffman
Robert M
RM
D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000556:secondary*; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000032:analysis*; D049452:Green Fluorescent Proteins; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000556:secondary*; D008164:Luminescent Proteins / Q000032:analysis*; D051379:Mice; D008819:Mice, Nude / Q000033:anatomy & histology*; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis*; D009368:Neoplasm Transplantation; D010781:Photography; D011993:Recombinant Fusion Proteins / Q000032:analysis; D014183:Transplantation, Heterologous
D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins