gms | German Medical Science

Objective: Acquired chemotherapy resistance is a persistent problem in treatment of cancer. Recently, Wnt16 came up as a relevant protein in development of cancer chemoresistance. It was found to be overexpressed in peritumoral tissue after chemotherapy in several non-CNS cancers like e.g. prostate and breast cancer contributing to enhanced tumor recovery and attenuated effects of further treatment. We investigated protein expression of Wnt16 in human gliomas before and after chemotherapy in tumors of different grades in order to find out if the described mechanism might play a role in glioma chemotherapy resistance as well.

Method: Western blot analysis was performed on tumor tissue samples from 27 patients with gliomas of different tumor grades and prior treatment. The differences between the three degrees of malignancy (WHO grade II-IV), primary and recurrent gliomas with and without chemotherapy were investigated. Bands were visualized using an enhanced chemoluminescent (ECL) kit (Sigma) on Bio-Rad ChemiDoc XRS system. Loading levels were normalized with β-actin and analyzed using ImageLab software. Currently results are being supplemented by quantitative real-time PCR of samples from 70 tumor patients. Besides, we are completing our study investigating effects of chemotherapeutics on Wnt16 with both, in primary glioma cell culture in vitro and in an animal model in vivo.

Results: Preliminary data of a first cohort indicate an elevated protein expression level in all tested tumors (see below) compared to control brain tissue (mean ± SEM: 0.35 ± 1.67). Contrarily to the published data, our first analysis of Wnt16 expression in glioblastomas show a decrease after chemotherapy, both in primary (without chemotherapy: mean ± SEM: 1.22 ± 0.14; after chemotherapy: 0.80 ± 0.30) and secondary glioblastomas (without chemotherapy: 1.22 ± 0.30; after chemotherapy: mean ± SEM: 0.61 ± 0.19). There was no obvious alteration of Wnt16 protein expression between different tumor grades (i.e. °II vs. °III vs. °IV).

Conclusions: Our data indicate that Wnt16 is overexpressed in gliomas and affected by chemotherapy. However, these data suggest that anti-glioma chemotherapy might not lead to the same mechanisms of chemoresistance due to Wnt16 activation in gliomas as observed in other tumor entities. Clarifying the underlying biological mechanism will provide more insight in a potentially clinically relevant role of Wnt16.