Background: Microenvironment is being increasingly recognized as a critical determinant in tumor progression and\nmetastasis. However, the appropriate regulatory mechanism to maintain the normal balance between differentiation\nand self-renewal of the cancer cell in microenvironment is not well known.\nMethods: 4T1 breast cancer cells were treated with embryonic stem (ES) cell conditioned medium which was\ncollected from mouse ES cells. Inhibition of tumor cell growth was based on the reduction of cell proliferation and\nviability, and inhibition of aggressive properties of tumor cells were examined using the wound-healing and\nmammosphere assays. The expression of stem cell-associated genes was detected by quantitative RT-PCR.\nResults: We used a real-time imaging system to investigate the effect of the mouse ES cell microenvironment on\naggressive breast cancer cells in vitro and in vivo. Exposure of breast cancer cells in mouse ES cell conditioned medium\nresulted in inhibition of growth, migration, metastasis, and angiogenesis of cancer cells. For many tumors, aggressive\nproperties were tightly related to Stat3 signaling activation. We specifically discovered that the ES cell\nmicroenvironment sufficiently suppressed Stat3 signaling pathway activation in aggressive tumor cells, leading to a\nreduction in tumorigenesis and invasiveness.\nConclusions: We identified important functions of Stat3 and their implications for antitumor effects of ES cell\nconditioned medium. Some factors secreted by ES cells could efficiently suppress Stat3 pathway activation in breast\ncancer cells, and were then involved in cancer cell growth, survival, invasion, and migration. This study may act as a\nplatform to understand tumor cell plasticity and may offer new therapeutic strategies to inhibit breast cancer\nprogression.
Loading....