Breast cancer is one of the leading causes of cancer related death in women, as a result of metastatic disease in vital organs. In the course of our studies into the mechanisms of breast metastasis, our group has identified a number of factors that regulate the process. Bone morphogenetic protein 4 (BMP4) is one of factors that potently suppresses breast cancer metastasis. The mechanism by which BMP4 suppresses metastasis is the focus of current research.
Sensitivity to anoikis, an important natural barrier of metastasis, is related to metastatic capacity. BMP4 is able to sensitise highly metastatic cancer cells to anoikis in a concentration dependent manner, indicating that BMP4 can act in an autocrine manner to reduce metastatic capacity.
Among mice bearing tumours from the syngeneic 4T1 model, splenomegaly and leukocytosis are observed in mice bearing the highly metastatic 4T1.2 tumour to a greater extent than in mice bearing 4T1.2 tumours with enforced BMP4 expression. BMP4 suppresses both expression and secretion of G-CSF in 4T1.2 cells, and thereby restricts the splenomegaly and leukocytosis of the tumour bearing mice. Recombinant G-CSF treatment expand the CD11b+Gr1+ myeloid derived suppressor cells (MDSC) in mice, facilitating the metastasis of weakly metastatic tumours. Forced expression of G-CSF in 4T1.2-BMP4 cells partially restores their metastatic capacity. These data indicate that BMP4 is able to modulate immune cytokine secretion and immune responses towards tumours, which may in turn prevent tumour cell dissemination.