No abstract

Glioblastoma (GBM) is one of the most malignant and devastating brain tumors. The presence of highly therapy‐resistant GBM cell subpopulations within the tumor mass, rapid invasion into brain tissues and reciprocal interactions with stromal cells in the tumor microenvironment contributes to an inevitable fatal prognosis for the patients. We highlight the most recent evidence of GBM cell crosstalk with mesenchymal stem cells (MSCs), which occurs either by direct cell–cell interactions via gap junctions and microtubules or cell fusion. MSCs and GBM paracrine interactions are commonly observed and involve cytokine signaling, regulating MSC tropism toward GBM, their intra‐tumoral distribution, and immune system responses. MSC‐promoted effects depending on their cytokine and receptor expression patterns are considered critical for GBM progression. MSC origin, tumor heterogeneity and plasticity may also determine the outcome of such interactions. Kinins and kinin‐B1 and ‐B2 receptors play important roles in information flow between MSCs and GBM cells. Kinin‐B1 receptor activity favors tumor migration and fusion of MSCs and GBM cells. Flow and image (tissue) cytometry are powerful tools to investigate GBM cell and MSC crosstalk and are applied to analyze and characterize several other cancer types.

Glioblastoma is the most lethal tumor of the central nervous system, presenting a very poor prognostic, with a survival around 16 months. The interaction of mesenchymal stem cells and tumor cells has been studied, showing a bias in their role favoring or going against aggressiveness. Natural products such as flavonoids have showed their anticancer properties and the synergic potential with the activation of microenvironment cells to inhibit tumor progression. Agathisflavone is a flavonoid studied in neurodegenerative diseases and cancer. The present study investigated the effect of flavonoid in the viability of heterogeneous glioblastoma (GBM) cells considering a coculture or conditioned medium of mesenchymal stem cells (MSCs) effect, as well as the dose‐dependent effect of this flavonoid in tumor migration and differentiation via STAT3. Agathisflavone (3–10 μM) induced dose‐dependent toxicity to GL‐15 and U373 human GBM cells, since 24 h after treatments. It was not toxic to human MSC but modified the pattern of interaction with GBM cells. Agathisflavone also inhibited migration and increased differentiation of human GBM cells, associated with the reduction on the expression of STAT3. These results demonstrate that the flavonoid agathisflavone had a direct anti‐glioma effect. However, could be observed its effect in MSCs response that may have an impact in controlling GBM growth and aggressiveness, an important factor to consider for new therapies.

No abstract

No abstract