Olfactory Receptors as Biomarkers in Human Breast Carcinoma Tissues.

Lea Weber,Stathis Philippou,Andrea Tannapfel,Christian Becker,Désirée Maßberg,Gabriele Bonatz,Gerhard Wölk,Günter Gisselmann,Burkhard Ubrig,Hanns Hatt,Janine Altmüller

doi:10.3389/fonc.2018.00033

Abstract

Olfactory receptors (ORs) are known to be expressed in a variety of human tissues and act on different physiological processes, such as cell migration, proliferation, or secretion and have been found to function as biomarkers for carcinoma tissues of prostate, lung, and small intestine. In this study, we analyzed the OR expression profiles of several different carcinoma tissues, with a focus on breast cancer. The expression of OR2B6 was detectable in breast carcinoma tissues; here, transcripts of OR2B6 were detected in 73% of all breast carcinoma cell lines and in over 80% of all of the breast carcinoma tissues analyzed. Interestingly, there was no expression of OR2B6 observed in healthy tissues. Immunohistochemical staining of OR2B6 in breast carcinoma tissues revealed a distinct staining pattern of carcinoma cells. Furthermore, we detected a fusion transcript containing part of the coding exon of OR2B6 as a part of a splice variant of the histone HIST1H2BO transcript. In addition, in cancer tissues and cell lines derived from lung, pancreas, and brain, OR expression patterns were compared to that of corresponding healthy tissues. The number of ORs detected in lung carcinoma tissues was significantly reduced in comparison to the surrounding healthy tissues. In pancreatic carcinoma tissues, OR4C6 was considerably more highly expressed in comparison to the respective healthy tissues. We detected OR2B6 as a potential biomarker for breast carcinoma tissues.

Highlights

Olfactory receptors (ORs) belong to the class of G-protein-coupled receptors, consisting of seven transmembrane domains
We analyzed the expression of ORs in 66 breast carcinoma tissues and cell lines and seven healthy breast tissues and ranked them according to their expression values (Figure 1)
OR2B6, had a pronounced expression in over 80% of all breast carcinoma tissues and 70% of all breast carcinoma cell lines, whereas it is not expressed in normal breast tissues (Figure 1C)

Summary

Introduction

Olfactory receptors (ORs) belong to the class of G-protein-coupled receptors, consisting of seven transmembrane domains. This superfamily contains approximately 380 functional OR genes, representing the largest gene family in humans [1, 2]. It was discovered by Linda Buck and Richard Axel as a gene family that was expressed in olfactory sensory neurons in the rat olfactory epithelium in 1991 [3]. In recent years, many milestones were set in the field of ectopic expression by the discovery of the receptor’s function outside of the nose.

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