The Neurokinin-1 Receptor Is Essential for the Viability of Human Glioma Cells: A Possible Target for Treating Glioblastoma.

BACKGROUND

Glioblastoma or glioma is the most common malignant brain tumor. Patients have a prognosis of approximately 15 months, despite the current aggressive treatment. Neurokinin-1 receptor (NK-1R) occurs naturally in human glioma, and it is necessary for the tumor development.

OBJECTIVE

The purpose of the study was to increase the knowledge about the involvement of the substance P (SP)/NK-1R system in human glioma.

METHODS

Cellular localization of NK-1R and SP was studied in GAMG and U-87 MG glioma cell lines by immunofluorescence. The contribution of both SP and NK-1R to the viability of these cells was also assessed after applying the tachykinin 1 receptor () or the tachykinin 1 () small interfering RNA gene silencing method, respectively.

RESULTS

Both SP and the NK-1R (full-length and truncated isoforms) were localized in the nucleus and cytoplasm of GAMG and U-87 MG glioma cells. The presence of full-length NK-1R isoform was mainly observed in the nucleus, while the level of truncated isoform was higher in the cytoplasm. Cell proliferation was decreased when glioma cells were transfected with siRNA, but not with . U-87 MG cells were more sensitive to the effect of the inhibition than GAMG cells. The decrease in the number of glioma cells after silencing of the siRNA gene was due to apoptotic and necrotic mechanisms. In human primary fibroblast cultured cells, silencing by siRNA did not produce any change in cell viability.

CONCLUSIONS

Our results show for the first time that the expression of the (NK-1R) is essential for the viability of GAMG and U-87 MG glioma cells. On the contrary, the is not essential for the viability of normal cells, confirming that NK-1R could be a promising and specific therapeutic target for the treatment of glioma.