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.