Peptide neurotoxins, small-cell lung carcinoma and neurological paraneoplastic syndromes

Peptide neurotoxins isolated from the venom of snakes, spiders and snails h ave represented invaluable tools for the identification and characterisatio n of membrane ion channels and receptors in vertebrate cells, including hum an neurons. We here report on the use of these toxins for the characterisat ion of membrane ion channels and receptors expressed by one of the most agg ressive human cancers, small-cell lung carcinoma. This tumour shares many p roperties with other neuro-endocrine cell types, including the ability of f iring action potentials and release hormones in a calcium-dependent manner. Toxins such as alpha -bungarotoxin and omega -conotoxins, among others, ha ve been successfully used to characterise neuronal nicotinic receptors and voltage-dependent calcium channels, respectively, in human small-cell lung carcinoma cells. These receptors and ion channels are not only crucial for the growth of this specific tumour, but also represent autoantigens against which cancer patients build an autoimmune response. Although the aim of th is autoimmune response is eventually the destruction of the cancer cells, t he circulating antibodies cross-react with similar ion channels and recepto rs present in normal neurons or other cells, causing a number of different paraneoplastic diseases, the best characterised of which is the Lambert-Eat on myasthenic syndrome. Conotoxin-based radioimmunoassays have become an in valuable tool for the diagnosis and follow up of these paraneoplastic disor ders and could represent a step forward in the early diagnosis of small-cel l lung carcinoma itself. (C) 2000 Societe francaise de biochimie et biologi e moleculaire / editions scientifiques et medicales Elsevier SAS.