*2.3. Transmission Electron Microscopy*

We used a transmission electron microscopy (TEM) protocol as previously described [41]. In more detail, tumor tissue was collected after sacrificing the animals. Tissue was cut into cubes of 2 mm<sup>3</sup> and fixed overnight in 2% glutaraldehyde and 0.05 M sodium cacodylate buffer (pH 7.3) at 4 ◦C. Tissue samples were post-fixed in 2% OsO4 in 0.05 M sodium cacodylate buffer (pH 7.3) for 1 h and stained with 2% uranyl acetate in 10% acetone for 20 min. Next, samples were dehydrated in graded concentrations of acetone and were embedded in epoxyresin (Araldite). Semi-thin slices (500 nm) were cut, stained with toluidine-blue and used for selecting regions of interest. Ultra-thin sections were mounted on 0.7% formvar coated grids, contrasted with uranyl acetate followed by lead citrate and examined with a Philips EM 208 transmission electron microscope operated at 80 kV. Digital images were taken with the MORADA 10/12 camera (Olympus, Hamburg, Germany). TEM analysis was performed with a Philips EM 208 S electron microscope (Philips, Eindhoven, The Netherlands). The microscope was provided with a Morada Soft Imaging System camera to acquire high resolution images of the evaluated samples. The images were processed digitally with the iTEM-FEI software (Olympus SIS, Münster, Germany).
