Human Glioma Migration and Infiltration Properties as a Target for Personalized Radiation Medicine

Abstract

Gliomas are primary brain tumors that present the majority of malignant adult brain tumors. Gliomas are subdivided into low- and high-grade tumors. Despite extensive research in recent years, the prognosis of malignant glioma patients remains poor. This is caused by naturally highly infiltrative capacities as well as high levels of radio- and chemoresistance. Additionally, it was shown that low linear energy transfer (LET) irradiation enhances migration and invasion of several glioma entities which might counteract today's treatment concepts. However, this finding is discussed controversially. In the era of personalized medicine, this controversial data might be attributed to the patient-specific heterogeneity that ultimately could be used for treatment. Thus, current developments in glioma therapy should be seen in the context of intrinsic and radiation-enhanced migration and invasion. Due to the natural heterogeneity of glioma cells and different radiation responses, a personalized radiation treatment concept is suggested and alternative radiation concepts are discussed.

Keywords: brain metastases; irradiation; migration and invasion; personalized medicine; primary brain tumor; radiotherapy; survival; treatment resistance; tumor heterogeneity.

Figure 1

Survival fraction of three patient-derived glioma cell lines (T76, H9, and H19). Shown are three survival curves fitted with the linear-quadratic model after low linear energy transfer (LET) irradiation. Each survival fraction was calculated from three different measurement sets (n = 3), and the standard error of the mean (SEM) is shown.

Figure 2

Invasion assay of primary patient-derived glioma cell lines. Shown are seven primary glioma cell lines that were examined for their invasion 24 h after 4 Gy X-ray irradiation. Each value represents the mean value of at least three biological replicates, and the SEM is depicted. Significance was calculated applying a Student’s t-test with * p ≤ 0.05 and ** p ≤ 0.01.