Translocator Protein (TSPO) as a Potential Biomarker in Human Cancers.

Nimisha Bhoola,Rodney Hull,Zukile Mbita,Zodwa Dlamini

doi:10.3390/ijms19082176

Abstract

TSPO is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed that the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer, and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney, and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of Tspo mRNA is not necessarily a good diagnostic biomarker in most cancers with changes not being large enough to be significantly different when detected by in situ hybridisation.

Highlights

The translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor [1], is an 18 kDa evolutionary conserved protein that was initially described as a binding site for benzodiazepine drugs outside of the central nervous system (CNS), but was later found to be expressed in every mammalian organ [2,3,4]
Nuclear localization of the Tspo mRNA occurred in some cases
Tspo mRNA was localized in the cytoplasm of cuboidal to low columnar epithelial cells lining glands and in the collagen fibres of the fibromuscular stroma and in the nuclei and cytoplasm of lymphocytes and endothelial cells lining blood vessels of the fibromuscular stroma of Grade II adenocarcinoma of the peripheral duct and acini (Figure 1E,F)

Summary

Introduction

The translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor [1], is an 18 kDa evolutionary conserved protein that was initially described as a binding site for benzodiazepine drugs outside of the central nervous system (CNS), but was later found to be expressed in every mammalian organ [2,3,4]. Despite its embryonic development and cholesterol transporter functions being central to our understanding of the physiological role of TSPO, these roles have recently been challenged [13,14,15]. Regardless of this a cholesterol recognition/interaction amino acid consensus (CRAC) sequence was identified as the cholesterol binding site based on an NMR structure of mouse TSPO [13]. TSPO is thought to be involved in Parkinson’s and Alzheimer’s diseases, inflammation, and tumour progression [13]

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