Radiation is part of standard therapies in clinical oncology due to its effective local tumor control and curative potential for many cancer types [
1,
2]. However, there were various observations in the earliest stages of radiation oncology that ineffective irradiation of solid tumors could ultimately result in the enhancement of metastasis [
3‐
7]. It is conceivable that the surviving cells, tumor cells as well as neighboring cells such as endothelial cells are modified phenotypically and genetically by irradiation. There is evidence in the literature that such surviving radiation-resistant tumor cells metastasize more frequently in animal models and could also lead to recurrence in patients [
8‐
12]. Every new formation of tumors – whether as local recurrence, as micrometastasis in the bone marrow or as distant metastasis – results from an interaction of the tumor cells with their environment [
9,
13‐
15]. Of particular importance here are the blood and lymph vessels [
16]. During the process of metastasis, the tumor cell first interacts with the endothelium, which slows down its speed (rolling) until it adheres locally (adhesion). Only then can the tumor cell leave the vessel and colonize new tissue [
17,
18]. Adhesion is therefore a decisive step in metastasis. In a similar way to the migration of 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]. However, it remains largely unclear how irradiation affects this cell-cell interaction and how the adhesion-associated proteins change. We have therefore 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. Breast cancer is one of the of most common tumor types that is well known to form local recurrences and metastases. Approximately 10% of all breast cancer patients have already developed verifiable distant metastases at the initial diagnosis and post-therapeutic metastases are not unusual [
21]. In contrast, 90% of cases of glioblastomas are characterized by local recurrences [
22,
23]. Nevertheless, both loco-regional and distant metastases are observed in some cases [
24]. Radiotherapy is commonly used as a treatment method for both tumor types. The differences in the metastatic properties of these two tumor entities could be of great clinical relevance with respect to whether irradiation affects adhesion of circulating tumor cells to the vascular endothelium. Special attention was also paid to focal adhesion kinase (FAK), which plays an important role in the regulation of integrin signaling, cell adhesion, migration and proliferation of cells. Decisive steps here are the autophosphorylation of FAK and its complex formation with paxillin and Src [
25‐
27]. In many tumor entities such as glioblastoma and breast cancer, FAK is often overexpressed, which correlates with increasing tumor malignancy [
28]. In addition to irradiation, we investigated the influence of an additional inhibition of FAK with the inhibitor PF-573, 228. This inhibitor inhibits phosphorylation and thus activation of FAK and its downstream effector paxillin and thus influences migration and adhesion [
29‐
33]. Our data show an increase in the adhesion of tumor cells to the endothelial cells after irradiation, which correlates with an upregulation of adhesion proteins. Phosphorylation of Src (Y416) and FAK (Y397) seems to play an important role and may potentially be inhibited by the inhibitor PF-573, 228, similarly to increased adhesion.