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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: r3d = −0.88 [−0.52;−0.97]; r4d = −0.90 [−0.59;−0.98].
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.
Abbreviations
| AFM | = | atomic force microscopy |
| CB | = | cannabinoid receptor |
| CFDA | = | fluorophores carboxyfluorescin diacetate |
| CTL | = | control |
| DAB | = | diaminobenzidine |
| eCB | = | endocannabinoid |
| FAK | = | focal adhesion kinase |
| FBS | = | fetal bovine serum |
| OHSC | = | organotypic hippocampal slice cultures |
| PBS | = | phosphate buffered saline |
| PI | = | propidium iodide |
| P/S | = | penicillin/streptomycin |
| THC | = | tetrahydrocannabinol |
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgments
The authors would like to thank Dr. Rene Keil and Prof. Mechtelt Hatzfeld for technical assistance, Prof. Ulrike Stein, Dr. Matthias Bache, Prof. Dirk Vordermark, and Prof. Thomas Groth for helpful discussions.
Funding
Support granted by Roux 29/18 Martin Luther University Halle-Wittenberg to U.G.
