Journal
ONCOLOGY REPORTS
Volume 33, Issue 6, Pages 2992-2998Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.3927
Keywords
breast cancer; metastasis; orthotopic model; lung; epithelial-mesenchymal transition
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Funding
- National '973' Program [2014CB932000]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB14000000]
- National Natural Science Foundation of China [21377159, 21177151, 21321004]
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Breast cancer is the second leading cause of cancer-related death among women, and distant metastasis is responsible for the death of similar to 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.
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