The influence of biomechanical properties and cannabinoids on tumor invasion

Abstract

Background: Cannabinoids are known to have an anti-tumorous effect, but the underlying mechanisms are only sparsely understood. Mechanical characteristics of tumor cells represent a promising marker to distinguish between tumor cells and the healthy tissue. We tested the hypothesis whether cannabinoids influence the tumor cell specific mechanical and migratory properties and if these factors are a prognostic marker for the invasiveness of tumor cells.Methods: 3 different glioblastoma cell lines were treated with cannabinoids and changes of mechanical and migratory properties of single cells were measured using atomic force microscopy and time lapse imaging. The invasiveness of cell lines was determined using a co-culture model with organotypic hippocampal slice cultures.Results: We found that cannabinoids are capable of influencing migratory and mechanical properties in a cell line specific manner. A network analysis revealed a correlation between a "generalized stiffness" and the invasiveness for all tumor cell lines after 3 and 4 d of invasion time: Conclusions: Here we could show that a "generalized stiffness" is a profound marker for the invasiveness of a tumor cell population in our model and thus might be of high clinical relevance for drug testing. Additionally cannabinoids were shown to be of potential use for therapeutic approaches of glioblastoma.

The Impact of Non-Lethal Single-Dose Radiation on Tumor Invasion and Cytoskeletal Properties

“…We found in our study that the generated composite parameter stiffness increased for both cell lines after irradiation. This parameter also correlates negatively with the measured invasiveness and agrees with the negative correlation of the composite parameter stiffness with the invasiveness found before by our lab [ 24 ]. This relation is further supported by the data obtained by other research groups, observing a negative correlation between cell stiffness and tumor aggressiveness in various tumor types, like mammary carcinoma, cervix carcinoma, prostate carcinoma, melanoma, etc.…”

“…The obtained parameter groupings were the same as published before and are given in the Figure S1, Tables S1 and S2 [ 24 ]. Most notably, the Young’s modulus and the indentation depth formed a cluster.…”

“…U87 and LN229 cells were obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA; U87: ATCC ® HTB-14 TM ; LN229: ATCC ® CRL-2611 TM ). Both cell lines were cultured as described elsewhere [ 24 ]. 24 h prior to the start of experiments, the culture medium was changed and the cells were irradiated with 2 Gy, with a dose rate of 2 Gy/min using 6 MV photons (Siemens, Erlangen, Germany, Siemens ONCOR).…”

“…The Western blot analysis was performed as described before [ 24 ]. The cells were collected in 75 µL of sample buffer.…”

“…Images were acquired every 5 min using a microscope (Leica, Wetzlar, Germany, Leica DMi 8) with temperature (37 °C) and CO 2 regulation (5% ( v / v )). The experiments were conducted as described previously and for the evaluation the parameters cell area, mean squared displacement, directionality, persistence time, persistence speed, and mean speed were measured (see Supplementary Materials ) [ 24 ].…”