The tumor microenvironment (TME) controls many aspects of cancer development but little is known about its effect in Glioblastoma (GBM), the main brain tumor in adults.
A group of researchers at Nantes (Frsnce) induced tumor-activated stromal cell (TASC) population, a component of TME in GBM, in vitro by incubation of MSCs with culture media conditioned by primary cultures of GBM under 3D/organoid conditions. They observed mitochondrial transfer by Tunneling Nanotubes (TNT), extracellular vesicles (EV) and cannibalism from the TASC to GBM and analyzed its effect on both proliferation and survival. The researchers created primary cultures of GBM or TASC in which they eliminated mitochondrial DNA [Rho 0 (r0) cells]. Then, they found that TASC, as described in other cancers, increased GBM proliferation and resistance to standard treatments (radio- therapy and chemotherapy). Finally, they analyzed the incorporation of purified mitochondria by r0 and rþ cells. MOLAB researchers studied the problem and derived a mathematical model showing that rþ cells incorporated more rapidly pure mitochondria than r0 cells.
Altogether, the results highlight the importance of cell-cell cooperation in tumors. This includes the transfer of material (including mitochondria) by different pathways: TNT, microvesicles and cannibalism of cells from the tumor microenvironment. The mechanisms implicated in the transfer of mitochondria to cancer cells might represent an important new therapeutic target in GBM.
Salaud et al., Mitochondria transfer from tumor-activated stromal cells (TASC) to primaryGlioblastomacells,Biochemical and Biophysical Research Communications, https://doi.org/10.1016/j.bbrc.2020.08.101