Sex differences in glioma growth – Do microglia or macrophages make the difference?
Edyta Motta (Berlin), Regine Piske (Berlin), Charlotte Flüh (Kiel; Berlin), Susanne Wolf (Berlin)
GBM is a highly malignant brain tumor with a devastating prognosis. Strikingly, men develop GBM more frequently and have a shorter survival than women. The reasons for this are currently unknown, and sex-specific treatment options are not available. Up to 40% of the tumor mass consist of glioma-associated microglia and macrophages (GAMs), which are known to foster glioma growth and invasiveness. Under physiologic conditions, microglia and macrophages harbor specific sex-dependent differences. In this study we aimed at evaluating whether there is a sex-specific influence of GAMs on glioma growth. We focused on circulation of sexual hormones, peripheral immune cells and the influence of sexual maturation on microglia.
We employed an ex vivo model of organotypic brain slices, using brains of P11- P14 mice pups, which were sectioned to 250µm coronal slices. Slices were transferred onto a semi-permeable membrane inserts with access to medium from the bottom. 72h after preparation, GL261-mCherry glioma cells were injected into each hemisphere. Tumor-inoculated OBS were cultivated for 5 day, fixated and analysed via confocal microscopy and the imaging analysis program IMARIS. Altering the model, estradiol was added to the culture medium, peripheral male or female monocytes were coinjected, and mature mice were chosen for slice generation. Statistical analysis was performed by using the Mann-Whitney test.
In slices harbouring only microglia, tumor volumes did not differ when comparing male and female slices (p=0,65). Tumors injected into slices of adult mice or additional treatment with the female sexual hormaone estradiol also did not show sex-dependent differences in tumor volume (p=0,9495). Coinjection of sex-specific bone-marrow derived monocytes resulted in significantly bigger tumors in males (p=0,0008).
Only if peripheral monocytes and microglia are present, a sex-specicifity in GAM-associatiated fostering of tumor growth can be observed, but not if only microglia are present. Maturity of microglia and presencence of estradiol does not affect tumor growth in sex-dependent manner. Caution has to be taken while interpreting data on sex-dependent differences coming from ex vivo models.
We use cookies on our website. Cookies are small (text) files that are created and stored on your device (e.g., smartphone, notebook, tablet, PC). Some of these cookies are technically necessary to operate the website, other cookies are used to extend the functionality of the website or for marketing purposes. Apart from the technically necessary cookies, you are free to allow or not allow cookies when visiting our website.