Affiliations: Division of Cell Biology and Experimental Cancer
Research, Institute of Pathology, University of Bern, Murtenstrasse 31, 3010
Bern, Switzerland | Ferring Research Institute, 3550 General Atomics
Court, Building 2, Room 442, San Diego, CA 92121, USA
Note: [] Corresponding author: Jean Claude Reubi, MD, Division of Cell
Biology and Experimental Cancer Research, Institute of Pathology, University of
Bern, PO Box 62, Murtenstrasse 31, CH-3010 Bern, Switzerland. Tel.: +41 31 632
3242; Fax: +41 31 632 8999; E-mail: reubi@pathology.unibe.ch
Abstract: Lung cancer is the leading cause of cancer death worldwide. The
overall 5-year survival after therapy is about 16% and there is a clear need
for better treatment options, such as therapies targeting specific molecular
structures. G-protein coupled receptors (GPCRs), as the largest family of cell
surface receptors, represent an important group of potential targets for
diagnostics and therapy. We therefore used laser capture microdissection and
GPCR-focused Affymetrix microarrays to examine the expression of 929 GPCR
transcripts in tissue samples of 10 patients with squamous cell carcinoma and 7
with adenocarcinoma in order to identify novel targets in non-small cell lung
carcinoma (NSCLC). The relative gene expression levels were calculated in
tumour samples compared to samples of the neighbouring alveolar tissue in every
patient. Based on this unique study design, we identified 5 significantly
overexpressed GPCRs in squamous cell carcinoma, in the following decreasing
order of expression: GPR87 > CMKOR1 >
FZD10 > LGR4 > P2RY11. All are
non-olfactory and GRAFS (glutamate, rhodopsin, adhesion,
frizzled/taste2, secretin family) classified. GPR87, LGR4 and CMKOR1 are
orphan receptors. GPR87 stands out as a candidate for further target validation
due to its marked overexpression and correlation on a mutation-based level to
squamous cell carcinoma.
