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.