Differential somatostatin, CXCR4 chemokine and endothelin A receptor expression in WHO grade I–IV astrocytic brain tumors
Glioblastomas represent the most common primary malignant tumor of the nervous system and the most frequent type of astrocytic tumors. Despite improved therapeutic options, prognosis has remained exceptionally poor over the last two decades. Therefore, new treatment approaches are urgently needed. An overexpression of somatostatin (SST) as well as chemokine CXCR4 and endothelin A (ETA) receptors has been shown for many types of cancer. Respective expression data for astrocytic brain tumors, however, are scarce and contradictory.
SST subtype, CXCR4 and ETA expression was comparatively evaluated in a total of 57 grade I–IV astrocytic tumor samples by immunohistochemistry using well-characterized monoclonal antibodies.
Overall, receptor expression on the tumor cells was only very low. SST5 was the most prominently expressed receptor, followed by SST3, ETA, SST2 and CXCR4. In contrast, tumor capillaries displayed strong SST2, SST3, SST5, CXCR4 and ETA expression. Presence of SST5, CXCR4 and ETA on tumor cells and of SST3, CXCR4 and ETA on microvessels gradually increased from grade II to grade IV tumors. Ki-67 values correlated significantly with CXCR4 expression on tumor cells and with vascular SST3, CXCR4 or ETA positivity. SST5 or CXCR4 positivity of tumor cells and vascular SST3 or CXCR4 expression negatively correlated with patient outcome.
Though having some prognostic value, SST, CXCR4 or ETA expression on astrocytic tumor cells is clearly of no therapeutic relevance. Indirect targeting of these highly vascularized tumors via SST3, SST5, CXCR4 or ETA on the microvessels, in contrast, may represent a promising additional therapeutic strategy.
KeywordsSomatostatin receptors CXCR4 Endothelin receptor A Astrocytoma Glioma Glioblastoma
C–X–C motif chemokine receptor 4
Endothelin receptor A
Conceived and designed the experiments: Daniel Kaemmerer, Amelie Lupp. Provided the tumor samples: Julianne Behnke-Mursch, Wolfgang Brück. Provided the antibodies: Stefan Schulz. Acquired the clinical data: Daniel Kaemmerer. Performed the experiments: Franziska Lange, Amelie Lupp. Analyzed the data: Franziska Lange, Amelie Lupp. Interpreted the data: Amelie Lupp. Wrote the paper: Amelie Lupp. Revised critically the manuscript: Franziska Lange, Daniel Kaemmerer, Julianne Behnke-Mursch, Wolfgang Brück, Stefan Schulz. Each of the authors has approved the manuscript and acknowledges that he or she participated sufficiently in the work to take public responsibility for its content.
The Theranostic Research Center, Zentralklinik Bad Berka, 99437 Bad Berka, Germany, provided funding for this research.
Compliance with ethical standards
Conflict of interest
Daniel Kaemmerer received funding and support for travelling to meetings by the companies Ipsen and Pfizer. All other authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Permission was gained from the local ethics committee (Ethikkommission der Landesärztekammer Thüringen) for this retrospective analysis. For this type of study formal consent is not required. All data were recorded and analyzed anonymously.
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