Artikel
Expression and function of cannabinoid receptors in human gliomas
Expression und Funktion der Cannabinoid-Rezeptoren in humanen Gliomen
Suche in Medline nach
Autoren
Veröffentlicht: | 8. Mai 2006 |
---|
Gliederung
Text
Objective: Cannabinoids are reported to inhibit the growth of tumors, including glioblastomas, in experimental laboratory animal models. The effects have been claimed to be mediated via cannabinoid receptor 1 and 2 (CB1, CB2).
Methods: We investigated the receptor subtype expression in surgical material of solid human astrocytomas, gliomas and in cultivated glioma cells by quantitative RT-PCR, Western blot, immunohistochemistry and assayed their functionality.
Results: In normal brain, cultivated glioma cells and solid tumors, CB1 mRNA was far higher expressed than CB2 that was even undetectable in some samples. Expression of both receptor subtypes was unrelated to malignancy, varied between the patients, and was not significantly increased in relation to normal brain tissues. In normal brain, CB1 protein was localized on astroglial and other cell types; in gliomas, it was found on highly proliferating (tumor-) as well as on non-malignant cells. CB2 protein was detected on microglial cells / macrophages and to a lesser extent on astroglial cells, both in normal and glioma tissue. Functionally, CB receptor agonists showed only minor anti-proliferative effects in vitro, although they potently reduced elevated cAMP levels in intact tumor tissue as well as in cultivated glioma cells.
Conclusions: We conclude that cannabinoid therapy of human gliomas targets not tumor-related receptors located on various cell types. Therefore, complex and potential side effects should be considered carefully.