Neurology Medical News about glioma growth;interleukin-6;vascular endothelial growth factor

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Combined targeting of interleukin-6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness
International Journal of Cancer, 05/12/09

Saidi A et al. - In a study to compare the effect of inhibiting interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) on U87-derived experimental glioma grown on the chick chorio-allantoic membrane (CAM) or in the brain of xenografted mice, it was reported that treatment with a combination of IL-6 and VEGF inhibitors brings synergistic antitumoral benefit and reduces global activity of major pathways of cell survival, proliferation, and invasiveness in remaining tumor cells that may be induced by using VEGF or IL-6 inhibitors alone.

Methods

The effect of inhibiting IL-6 and VEGF was compared in U87-derived experimental glioma grown on the chick CAM or in the brain of xenografted mice.
Tumor growth was monitored by biomicroscopy and immunohistology.

Results

In vitro, IL-6 knockdown had no effect on proliferation but substantially enhanced invasion.
In the CAM experimental glioma, IL-6 or VEGF knockdown reduced growth and vascularization of the tumors with a comparable efficiency, but increased invasion of residual tumor cells.
Combined IL-6/VEGF knockdown not only showed enhanced reduction of tumor growth and angiogenesis but also significantly prevented invasion of residual tumor cells.
In mice, combining IL-6 knockdown and bevacizumab treatment completely abrogated tumor development and infiltration.
Molecular response of tumor cells to single or combined treatment was studied by transcriptomic profiling.
Many cell cycle-promoting genes and chromatin components were silenced in the double knockdown.
Specific migratory signatures detected in tumors under single IL-6 or VEGF knockdown were partially erased in combined IL-6/VEGF knockdown tumors.

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