Olfactory receptor 51E1 protein as a potential novel tissue biomarker for small intestine neuroendocrine carcinomas

Abstract

Objective: Late diagnosis hinders proper management of small intestine neuroendocrine carcinoma (SI-NEC) patients. The olfactory receptor, family 51, subfamily E, member 1 (OR51E1) has been reported as a potential novel SI-NEC marker, without protein expression recognition. Thus, we further studied whether the encoded protein may be a novel SI-NEC clinical biomarker. Design: OR51E1 coding sequence was cloned using total RNA from SI-NEC patient specimens. Quantitative real-time PCR analysis explored OR51E1 expression in laser capture microdissected SI-NEC cells and adjacent microenvironment cells. Moreover, immunohistochemistry investigated OR51E1 protein expression on operation and biopsy material from primary SI-NECs, mesentery, and liver metastases from 70 patients. Furthermore, double immunofluorescence studies explored the potential co-localization of the vesicular monoamine transporter 1 (SLC18A1, generally referred to as VMAT1) and OR51E1 in the neoplastic cells and in the intestinal mucosa adjacent to the tumor. Results: OR51E1 coding sequence analysis showed absence of mutation in SI-NEC patients at different stages of disease. OR51E1 expression was higher in microdissected SI-NEC cells than in the adjacent microenvironment cells. Furthermore, both membranous and cytoplasmic OR51E1 immunostaining patterns were detected in both primary SI-NECs and metastases. Briefly, 18/43 primary tumors, 7/28 mesentery metastases, and 6/18 liver metastases were 'positive' for OR51E1 in more than 50% of the tumor cells. In addition, co-localization studies showed that OR51E1 was expressed in O50% of the VMAT1 immunoreactive tumor cells and of the enterochromaffin cells in the intestinal mucosa adjacent to the tumor. Conclusion: OR51E1 protein is a potential novel clinical tissue biomarker for SI-NECs. Moreover, we suggest its potential therapeutic molecular target development using solid tumor radioimmunotherapy.

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer–Initiating Cells and Is a Potent Target of Immunotherapy

“…A previous study showed that an olfactory receptor, OR51E2, is expressed in prostate cancer cells and that activation of OR51E2 by its ligand, b-ionone and inhibited proliferation of prostate cancer cells (29). Another olfactory receptor family member, OR51E1, was reported to be a potential novel biomarker for small intestine neuroendocrine carcinoma (30). Expression of the olfactory receptor OR13C4 was shown to be significantly associated with risk of pancreatic cancer by pathway analysis in a genome-wide association study (31).…”

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

“…Their discovery sparked a controversial discussion about the potential function of such “ectopically expressed” ORs. Many groups have reported mammalian OR expression at the transcript and/or protein level in various healthy as well as pathophysiologically altered tissues such as prostate cancer [19, 25, 31, 34, 70, 101, 105, 109, 111, 115]. …”

Olfactory receptor 51E1 as a novel target for diagnosis in somatostatin receptor-negative lung carcinoids

“…OR51E1 mRNA expression has been detected in normal brain (Vanti et al 2003) and prostate tissue (Weigle et al 2004). Furthermore, cancer cells, such as prostate carcinoma cells (Weigle et al 2004, Fuessel et al 2006 and small intestine neuroendocrine carcinoma (SI-NEC) cells (Leja et al 2009, Cui et al 2013, have been shown to express high levels of OR51E1. The pathophysiological role of OR51E1 in tumorigenesis and tumor progression has not been elucidated.…”