Abstract
BackgroundRadiotherapy is administered in more than 60% of all solid tumors. Most patients are cured but a significant number develops local recurrences or distant metastases. The question arises if irradiation might influence the metastatic process. In the present study we examined whether the adhesion of glioblastoma or breast cancer cells to endothelial cells, an important step in metastasis, is affected by photon irradiation.MethodsU-87 MG, U-373 MG and MDA-MB-231 cancer cells as well as primary human endothelial cells were irradiated with 0, 2, 4, or 8 Gy photons at a dose rate of 5 Gy/min. The adhesion of cancer cells to endothelial cells was tested either with the Vybrant based assay via fluorescent labelling or with an ibidi pump system able to mimic the physiological blood flow in vitro. In addition, the impact of FAK (focal adhesion kinase) inhibitor PF-573, 228 on the adhesion of non-irradiated and irradiated tumor cells was analyzed. Adhesion related and regulated proteins were analyzed by Western blotting.ResultsThe cellular adhesion was increased after irradiation regardless of which cell type was irradiated. The FAK-inhibitor was able to reduce the adhesion of non-irradiated cells but also the irradiation-induced increase in adhesion of tumor cells to endothelium. Adhesion related proteins were enhanced after irradiation with 4 Gy or 8 Gy in both cells types. The increased adhesion after irradiation is accompanied by the phosphorylation of src (Y416), FAK (Y397) and increased expression of paxillin.ConclusionIrradiation with photons in therapeutic doses is able to enhance the interaction between tumor cells and endothelial cells and by that might influence important steps of the metastatic process.
Highlights
Radiotherapy is administered in more than 60% of all solid tumors
We have used various macroscopic methods to investigate whether and how irradiation with photons alters the adhesion of breast cancer cells or glioblastoma cells to an endothelial cell monolayer and whether this is reflected in the expression of associated proteins
Special attention was paid to focal adhesion kinase (FAK), which plays an important role in the regulation of integrin signaling, cell adhesion, migration and proliferation of cells
Summary
Radiotherapy is administered in more than 60% of all solid tumors. Most patients are cured but a significant number develops local recurrences or distant metastases. In the present study we examined whether the adhesion of glioblastoma or breast cancer cells to endothelial cells, an important step in metastasis, is affected by photon irradiation. Nguemgo Kouam et al Radiation Oncology (2019) 14:25 leukocytes from the vessel in response to inflammatory processes, the adhesion of tumor cells is regulated by certain surface molecules. This adhesion can take place directly between tumor cells and endothelium with the help of adhesion-associated proteins or indirectly via leukocytes [19, 20]. Phosphorylation of Src (Y416) and FAK (Y397) seems to play an important role and may potentially be inhibited by the inhibitor PF-573, 228, to increased adhesion
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