Abstract
Certain cancers exert unexplained remote effects on the nervous system1. Small cell carcinoma (SCC) of the lung, a tumour capable of spike electrogenesis2 and which is of possible neural crest origin3, is present in ∼70% of patients with the Lambert-Eaton myasthenic syndrome (LEMS)4, a disorder characterized by fatigable muscle weakness. Patients with this syndrome have a defect in the (Ca2+-dependent) quantal release of acetylcholine from motor nerve terminals evoked by a nerve impulse or by high K+ (ref. 5), and a decreased number of presynaptic active zone particles6. The physiological and morphological features of the syndrome can be transferred to mice by the patients' IgG, consistent with an autoantibody interfering with the function of voltage-dependent Ca2+ channels7–10. Here we demonstrate that K+-induced 45Ca2+ flux in a cultured human SCC line is significantly reduced by LEMS IgG, suggesting that in SCC-LEMS an autoantibody to tumour Ca2+-channel determinants is triggered; its cross-reaction with similar determinants at the motor nerve terminal could lead to the remote neurological syndrome.
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Roberts, A., Perera, S., Lang, B. et al. Paraneoplastic myasthenic syndrome IgG inhibits 45Ca2+ flux in a human small cell carcinoma line. Nature 317, 737–739 (1985). https://doi.org/10.1038/317737a0
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DOI: https://doi.org/10.1038/317737a0
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