Department of Oncology, Faculty of Medicine, University of Calgary, 1331 29 St, NW, Calgary, AB T2N 4N2, Canada.
Breast Cancer Res Treat. 2012 May;133(1):201-14. doi: 10.1007/s10549-011-1753-2. Epub 2011 Sep 6.
The preferential metastasis of breast cancer cells to bone comprises a complex set of events including homing and preferential growth, which may require unique factors produced by bone or other cells in the immediate microenvironment. In this study, an in vitro co-culture system composed of bone mesenchymal stem cells and breast cancer cell lines is used to examine the role of Src kinase on breast cancer cell migration and invasion in the presence of bone-derived cells. This research shows that Src kinase activity in breast cancer cell lines with either high or low levels of endogenous Src activity is increased by bone-derived cell-conditioned medium but not HS68 fibroblast-conditioned medium. Breast cancer cells exhibit enhanced migration in co-culture with bone-derived cells but not HS68 fibroblasts or no co-cultured cells. Inhibition of Src kinase activity using the inhibitors PP2 or saracatinib or using siRNA abrogates the preferential migration of the breast cancer cell lines in response to bone-derived cells. Inhibition of Src activity with saracatinib does not have any significant effect on breast cancer cell invasion in the presence of bone-derived cells. Factors are identified that are produced preferentially by bone-derived cells over HS68 cells that may impact breast cancer cell behavior. This research implicates Src kinase as an important effector of bone-derived cell signals on breast cancer cell migration.
乳腺癌细胞优先转移到骨骼包括一系列复杂的事件，包括归巢和优先生长，这可能需要骨骼或其他细胞在直接微环境中产生独特的因子。在这项研究中，使用由骨髓间充质干细胞和乳腺癌细胞系组成的体外共培养系统，研究了 Src 激酶在骨源性细胞存在下对乳腺癌细胞迁移和侵袭的作用。研究表明，高或低内源性 Src 活性的乳腺癌细胞系中 Src 激酶活性被骨源性细胞条件培养基增加，但不被 HS68 成纤维细胞条件培养基增加。乳腺癌细胞在与骨源性细胞共培养时表现出增强的迁移，但与 HS68 成纤维细胞或无共培养细胞则没有。使用抑制剂 PP2 或 saracatinib 抑制 Src 激酶活性或使用 siRNA 阻断乳腺癌细胞系对骨源性细胞的优先迁移。在骨源性细胞存在的情况下，saracatinib 抑制 Src 活性对乳腺癌细胞侵袭没有任何显著影响。鉴定出骨源性细胞比 HS68 细胞优先产生的可能影响乳腺癌细胞行为的因子。这项研究表明 Src 激酶是骨源性细胞信号对乳腺癌细胞迁移的重要效应因子。
