Wie beeinflusst Bestrahlung der extrazellulären Matrix das Invasionsverhalten von Nierenzellkarzinomen?
by Verena Vittoria Macri
Date of Examination:2025-12-09
Date of issue:2025-12-02
Advisor:Prof. Dr. Arndt F. Schilling
Referee:Prof. Dr. Fred S. Wouters-Bunt
Referee:Prof. Dr. Günter Schneider
Persistent Address:
http://dx.doi.org/10.53846/goediss-11641
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Abstract
English
Renal cell carcinoma often forms bone metastases and is often only discovered in late stages due to metastasis-associated symptoms. Affected patients suffer from pain, the survival rates are poor. Thanks to new techniques such as stereotactic radiation, radiation therapy is becoming increasingly important in the treatment of renal cell carcinoma. In radiation therapy the cancer cells surrounding tissue is irradiated as well as the cancer cells. The surrounding tissue mostly consists of extracellular matrix (ECM). The ECM functions as a barrier to cancer cell metastasis by forming basement membranes. In this study we built an artificial basement membrane by using Matrigel. We studied in how far the invasion of renal cell cancer cells through an artificial basement membrane was effected by radiation of said membrane. Our invasion experiments using the xCELLigence Real Time Cell Analysis Dual Purpose System show that radiation of a Matrigel membrane can inhibit the invasion of the renal cell carcinoma cell line 786-O through this membrane. This effect occurred at doses of 25 Gy and above - no significant effect was observed at 12.5 Gy. The exact reason for the inhibition is yet to be discovered. Previous research results suggest an interaction between radiation and collagen present in ECM. Collagen appears to be softened by the radiation, which seems to have a negative effect on the invasion of cancer cells. In our experiments, we focused on laminin-1, which was analysed using Western Blot. As a heterotrimer, laminin-1 consists of three subunits: α1, β1, and γ1. The analyses showed that the band pattern of irradiated laminin intensified with increasing radiation dose. We suspect radiation to destroy laminin’s structure. This effect could only be observed in Western Blot analyses in which the used antibody was directed against the entire laminin protein. The analyses with antibodies against the subunits α1, β1, and γ1 showed no significant differences due to radiation. Furthermore, a significant effect of radiation in the Western Blot could only be found in relation to laminin within Matrigel. No significant change was observed in pure laminin. Laminin could be blocked by collagen in non-irradiated Matrigel and thus not be accessible to the Western Blot antibodies. Radiation can lead to unmasking, making laminin accessible to the antibodies and allowing it to exert an inhibitory effect on the renal cell carcinoma cells. Understanding the effects of radiation on tissue surrounding tumors and the extent to which it has a positive or negative impact on the metastasis of various tumor entities can contribute to optimizing individual tumor therapy for patients and improve survival rates in the future.
Keywords: Renal Cell Cancer; Radiation; Extracellular Matrix; xCELLigence; Bone Metastases; Matrigel; Basement Membrane
