Figure 5. Vascular responses to Ca²⁺ uncaging in astrocytes is impaired in vessels co-opted by glioma cells.

[Ca²⁺]_i uncaging in an astrocyte endfoot or cell body close to an arteriole free of glioma cells leads to either constriction (a) or dilation (c) of the vessel. The vessel response is preceded by a rise in [Ca²⁺]_i (b,d). The pink spot indicates the location of Ca2+ uncaging. Measurement of the Ca²⁺ response was performed in this region or in an immediate adjacent region. Vessels encased by glioma cells do not respond to Ca²⁺ uncaging in nearby astrocytes (e,f). Stimulation of astrocytes in tumor-free areas of the same vessel (downstream vessel area) causes constriction showing that the lack of response is specific for areas covered by glioma cells (f,g). The cumulative relative frequency distribution shows a wide range of dilatory or constricting vessel responses in controls, whereas most vessels associated with glioma do not respond or do so to a lesser extent (h). Statistical data in d: control dilating vessels, 60.05 ± 8.899 %, n=10 vessels, tumor dilating, 5.18 ± 1.493, n=8, two-tailed unpaired t-test, p ≤ 0.0001; control constricting vessels, -43.51 ± 6.283 % n=18 vessels, glioma constricting, -9.389 ± 2.611 %, n=9. two-tailed unpaired t-test, p≤ 0.001, error bars refer to SEM.

Scale, 20 μm.