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 fur exocytosis of biogenic amines by neurons and endocrine cells. In this study, we examined whether these pr oteins exist in high-grade malignant small cell lung carcinomas (SCLCs), la rge cell carcinomas, adenocarcinomas, and squamous cell carcinomas of the l ung. 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-fr ozen SCLC samples (n = 2), Using immunocytochemistry, Western blotting, Nor thern 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 confi rmed by RT-PCR performed with material extracted from paraffin sections, We stern blot analysis and RT-PCR carried out with snap-frozen SCLC tumors rev ealed the presence of SNAREs and VMATs, Immunohistochemistry showed that no n-SCLC tumors were negative for SNAREs and VMATs, with the exception of imm unostaining fur SNAP-25 and syntaxin1 in 3 of 10 adenocarcinomas. Our findi ngs indicate that SCLC cells are endowed with transporters necessary for in tracellular storage of biogenic amines and with proteins required for exocy tosis of secretory products. These proteins may be used as markers of diffe rentiation of human lung tumors. Moreover, the presence of VMATs provides t he basis for a diagnostic application of biogenic amine-derived tracers in positron emission tomography of SCLC tumors.