Expression of vesicular monoamine transporters, synaptosomal-associated protein 25 and syntaxin1 : A signature of human small cell lung carcinoma

Vesicular monoamine transporters (VMATs) are a prerequisite for the uptake of biogenic amines into intracellular storage organelles, whereas soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs; such as SNAP-25 and syntaxin1) are essential for exocytosis of biogenic amines...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2001-03, Vol.61 (5), p.2138-2144
Main Authors: GRAFF, Lothar, CASTROP, Florian, BAUER, Markus, HÖFLER, Heinz, GRATZL, Manfred
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Antigens, Surface - biosynthesis
Antigens, Surface - genetics
Biological and medical sciences
Biomarkers, Tumor - biosynthesis
Biomarkers, Tumor - genetics
Blotting, Northern
Carcinoma, Small Cell - genetics
Carcinoma, Small Cell - metabolism
Humans
Immunohistochemistry
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Medical sciences
Membrane Glycoproteins - biosynthesis
Membrane Glycoproteins - genetics
Membrane Proteins
Membrane Transport Proteins
Nerve Tissue Proteins - biosynthesis
Nerve Tissue Proteins - genetics
Neuropeptides
Pneumology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Synaptosomal-Associated Protein 25
Syntaxin 1
Tumor Cells, Cultured
Tumors of the respiratory system and mediastinum
Vesicular Biogenic Amine Transport Proteins
Vesicular Monoamine Transport Proteins
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Summary:Vesicular monoamine transporters (VMATs) are a prerequisite for the uptake of biogenic amines into intracellular storage organelles, whereas soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs; such as SNAP-25 and syntaxin1) are essential for exocytosis of biogenic amines by neurons and endocrine cells. In this study, we examined whether these proteins exist in high-grade malignant small cell lung carcinomas (SCLCs), large cell carcinomas, adenocarcinomas, and squamous cell carcinomas of the lung. We analyzed two established human SCLC cell lines, one adenocarcinoma cell line, paraffin-embedded tumors (SCLC, n = 25; large cell carcinoma, n = 10; adenocarcinoma, n = 10; squamous cell carcinoma, n = 10), and snap-frozen SCLC samples (n = 2). Using immunocytochemistry, Western blotting, Northern blotting, RT-PCR, and sequencing, we identified VMAT1, VMAT2, SNAP-25, and syntaxin1 in cultured SCLC cells. Immunohistochemistry carried out on paraffin sections revealed that all SCLC tumors express VMAT1, VMAT2, SNAP-25, and syntaxin1. The presence of SNAP-25 and syntaxin1 in SCLC was confirmed by RT-PCR performed with material extracted from paraffin sections. Western blot analysis and RT-PCR carried out with snap-frozen SCLC tumors revealed the presence of SNAREs and VMATs. Immunohistochemistry showed that non-SCLC tumors were negative for SNAREs and VMATs, with the exception of immunostaining for SNAP-25 and syntaxin1 in 3 of 10 adenocarcinomas. Our findings indicate that SCLC cells are endowed with transporters necessary for intracellular storage of biogenic amines and with proteins required for exocytosis of secretory products. These proteins may be used as markers of differentiation of human lung tumors. Moreover, the presence of VMATs provides the basis for a diagnostic application of biogenic amine-derived tracers in positron emission tomography of SCLC tumors.
ISSN:0008-5472
1538-7445