title: Establishment of a novel orthotopic model of breast cancer metastasis to the lung.
abstract: Breast cancer is the second leading cause of cancer-related death among women, and distant metastasis is responsible for the death of ~90% of these patients. However, despite recent advances, the underlying mechanisms responsible for breast cancer metastasis remain elusive. A great impediment to this is the lack of appropriate orthotopic models of breast cancer metastasis to distant organs. In the present study, we established a novel orthotopic model of breast cancer metastasis to the lungs in mice, where metastatic sublines of 4T1 cells revealed enhanced metastatic propensity to the lungs. All mice (100%) developed lung metastasis upon orthotopic implantation of a metastatic subline of 4T1 cells, in contrast to 10% of mice with lung metastasis for a subline derived from primary tumors and 60% of mice with lung metastasis for parental 4T1 cells. At the molecular level, significant epithelial-mesenchymal transition was characterized in these metastatic sublines, which is likely at least partially, responsible for the enhanced metastasis. These established cell lines provide a novel platform to study the relevant molecular basis of metastasis and metastasis-specific therapeutics.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco‑Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P.R. China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Guo
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco‑Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, P.R. China.
authors.forename: Sijin
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation