Basic and clinical aspects of non-neuronal acetylcholine: Expression of non-neuronal acetylcholine in lung cancer provides a new target for cancer therapy

Pingfang Song, Eliot Spindel

    Research output: Contribution to journalArticle

    52 Citations (Scopus)

    Abstract

    Lung cancer is the leading cause of cancer death worldwide and new treatment strategies are clearly needed. The recent discovery that lung and other cancers synthesize and secrete acetylcholine (ACh) which acts as an autocrine growth factor suggests that this cholinergic autocrine loop may present new therapeutic targets. In normal bronchial epithelium, small airway epithelium and pulmonary neuroendocrine cells synthesize Ach; and in squamous cell lung carcinoma, adenocarcinoma, and small cell lung carcinoma, the respective lung cancers that derive from those cell types similarly synthesize ACh. ACh secreted by those cancers stimulates growth of the tumors by binding to nicotinic and muscarinic receptors expressed on lung cancers. Thus antagonists to nicotinic and muscarinic receptors can inhibit lung cancer growth. The muscarinic receptor (mAChR) subtype utilized for cell proliferation is the M3 subtype and consistent with this M3 mAChR antagonists inhibit growth of SCLC and squamous cell carcinomas. This is significant as M3 mAChR antagonists have low toxicity and are in wide clinical use. As multiple other cancer types besides lung carcinomas express both M 3 mAChR and acetylcholine, other cancer types besides lung carcinoma may respond to M3 mAChR antagonists.

    Original languageEnglish (US)
    Pages (from-to)180-185
    Number of pages6
    JournalJournal of Pharmacological Sciences
    Volume106
    Issue number2
    DOIs
    StatePublished - 2008

    Fingerprint

    Acetylcholine
    Lung Neoplasms
    Muscarinic Receptors
    Neoplasms
    Nicotinic Receptors
    Therapeutics
    Squamous Cell Carcinoma
    Epithelium
    Growth
    Carcinoma
    Neuroendocrine Cells
    Small Cell Lung Carcinoma
    Cholinergic Agents
    Cause of Death
    Intercellular Signaling Peptides and Proteins
    Cell Proliferation
    Lung

    Keywords

    • Cancer
    • Lung cancer
    • Muscarinic receptor
    • Nicotinic receptor
    • Non-neuronal acetylcholine
    • Non-neuronal cholinergic system

    ASJC Scopus subject areas

    • Pharmacology
    • Molecular Medicine

    Cite this

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    title = "Basic and clinical aspects of non-neuronal acetylcholine: Expression of non-neuronal acetylcholine in lung cancer provides a new target for cancer therapy",
    abstract = "Lung cancer is the leading cause of cancer death worldwide and new treatment strategies are clearly needed. The recent discovery that lung and other cancers synthesize and secrete acetylcholine (ACh) which acts as an autocrine growth factor suggests that this cholinergic autocrine loop may present new therapeutic targets. In normal bronchial epithelium, small airway epithelium and pulmonary neuroendocrine cells synthesize Ach; and in squamous cell lung carcinoma, adenocarcinoma, and small cell lung carcinoma, the respective lung cancers that derive from those cell types similarly synthesize ACh. ACh secreted by those cancers stimulates growth of the tumors by binding to nicotinic and muscarinic receptors expressed on lung cancers. Thus antagonists to nicotinic and muscarinic receptors can inhibit lung cancer growth. The muscarinic receptor (mAChR) subtype utilized for cell proliferation is the M3 subtype and consistent with this M3 mAChR antagonists inhibit growth of SCLC and squamous cell carcinomas. This is significant as M3 mAChR antagonists have low toxicity and are in wide clinical use. As multiple other cancer types besides lung carcinomas express both M 3 mAChR and acetylcholine, other cancer types besides lung carcinoma may respond to M3 mAChR antagonists.",
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    AB - Lung cancer is the leading cause of cancer death worldwide and new treatment strategies are clearly needed. The recent discovery that lung and other cancers synthesize and secrete acetylcholine (ACh) which acts as an autocrine growth factor suggests that this cholinergic autocrine loop may present new therapeutic targets. In normal bronchial epithelium, small airway epithelium and pulmonary neuroendocrine cells synthesize Ach; and in squamous cell lung carcinoma, adenocarcinoma, and small cell lung carcinoma, the respective lung cancers that derive from those cell types similarly synthesize ACh. ACh secreted by those cancers stimulates growth of the tumors by binding to nicotinic and muscarinic receptors expressed on lung cancers. Thus antagonists to nicotinic and muscarinic receptors can inhibit lung cancer growth. The muscarinic receptor (mAChR) subtype utilized for cell proliferation is the M3 subtype and consistent with this M3 mAChR antagonists inhibit growth of SCLC and squamous cell carcinomas. This is significant as M3 mAChR antagonists have low toxicity and are in wide clinical use. As multiple other cancer types besides lung carcinomas express both M 3 mAChR and acetylcholine, other cancer types besides lung carcinoma may respond to M3 mAChR antagonists.

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    KW - Non-neuronal cholinergic system

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