Article
Inhibition of tumour angiogenesis by the anti-ageing protein Klotho in glioblastoma
Hemmung von Tumorangiogenese durch das Anti-Altertums-Eiweiß Klotho in Glioblastom
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Published: | June 4, 2021 |
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Objective: Klotho is a kidney-derived protein that has been shown to exert anti-tumor effects in a variety of malignancies. To date, the inhibition of tumor cell proliferation, the induction of apoptosis, the inhibition of tumor cells migration, and the induction of autophagy have been identified as the responsible mechanisms. It is unknown, however, whether Klotho can inhibit tumor angiogenesis. To assess whether Klotho inhibits tumor angiogenesis, we explored the effects of exogenous Klotho stimulation in glioblastoma (GBM) models, since GBM is amongst the most vascularized solid cancers.
Methods: We investigated the indirect, GBM cell-mediated, effects of exogenous Klotho stimulation in in vitro tube formation assays and in the in ovo chorioallantoic membrane (CAM) model (N = 11-14 eggs per group).
Results: We found that Klotho-treated GBM cell-conditioned medium (U251, U87 and GSC23 cells) significantly inhibited tube formation in vitro. Supernatants from Klotho-stimulated GBM cells (U87 and GSC23) reduced in ovo capillary vascularization by 45% and 36%, respectively, compared to PBS-stimulated control groups.
Conclusion: In short, we found that Klotho acts as an inhibitor of GBM-induced angiogenesis in vitro and in ovo. These data comprise the first indication that Klotho inhibits tumor angiogenesis. Furthermore, these data indicate that the potential for Klotho-based treatments merits further research.