The Role of Catecholamines in Lung Cancer

儿茶酚胺在肺癌中的作用

• 批准号: 9153980
• 负责人: Brid Ryan
• 金额: $ 60.98万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9153980
• 关键词: Alzheimer' s Disease; Angiogenesis Inhibitors; Animal Model; Brain; Bronchi; CD8B1 gene; Cancer Patient; Catecholamines; Cells; Data; Dopamine; Dopamine Agonists; Dopamine Antagonists; Dopamine Receptor; Epidemiology; Family; Horns; Human; Immune system; Link; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Maps; Metabolism; Molecular; Monograph; Outcome; Parkinson Disease; Patients; Pattern; Pharmaceutical Preparations; Play; Publishing; Research; Respiration; Risk; Role; Schizophrenia; Seminal; Signal Transduction; Smoking; Structure of parenchyma of lung; T-Lymphocyte; Therapeutic Agents; Tumor Suppressor Proteins; Work; base; bone; cancer therapy; carcinogenesis; follow-up; immunoreactivity; nervous system disorder; receptor

While dopamine signaling and its receptors are well characterized in the brain, there is a paucity of data regarding the role and the expression pattern of dopamine and its receptors in the normal lung. Previous studies have shown that dopamine plays an important role in bronchi-dilation and respiration, however a comprehensive analysis of dopamine, its receptors, transporters and metabolism has not been conducted. We are therefore mapping the dopamine axis in both normal lung tissue and human lung cancer. Our initial studies suggest that certain subtypes of the dopamine receptor family may function as tumor suppressors and we are currently validating those observations and investigating the molecular mechanism. In addition, we are examining the efficacy of specific dopamine receptor agonists and antagonists as therapeutic agents against cancer. We will also evaluate the effect of dopamine on the immune system in these animal models of lung cancer as, in addition to functioning as an inhibitor of angiogenesis, recent work shows that CD4 and CD8 T cells express dopamine receptors. Moreover, these cells synthesize and transport dopamine. T cells from patients with PD have reduced dopamine receptor immunoreactivity, suggesting that the connection between dopamine and cancer could involve the immune system. We are also conducting an analysis of anti-depressant use among lung cancer patients to ask whether these patients have a better or worse outcome compared to those not taking anti-depressants. As many anti-depressants function as dopamine agnonists and antagonists, if dopamine is a bone fide tumor suppressor, this research could have implications for repositioning of this drug class towards cancer treatment.

虽然多巴胺信号传导及其受体在大脑中得到了很好的表征，但关于多巴胺及其受体在正常肺中的作用和表达模式的数据很少。以往的研究表明，多巴胺在支气管扩张和呼吸中起着重要作用，但尚未对多巴胺及其受体、转运蛋白和代谢进行全面分析。因此，我们正在绘制正常肺组织和人类肺癌中的多巴胺轴。我们的初步研究表明，多巴胺受体家族的某些亚型可能具有肿瘤抑制剂的功能，我们目前正在验证这些观察结果并研究分子机制。此外，我们正在研究特定多巴胺受体激动剂和拮抗剂作为癌症治疗剂的疗效。我们还将在这些肺癌动物模型中评估多巴胺对免疫系统的影响，因为除了作为血管生成抑制剂外，最近的工作表明CD4和CD8 T细胞表达多巴胺受体。此外，这些细胞合成和运输多巴胺。来自PD患者的T细胞具有降低的多巴胺受体免疫反应性，这表明多巴胺和癌症之间的联系可能涉及免疫系统。我们还在肺癌患者中进行抗抑郁药使用的分析，以询问这些患者与未服用抗抑郁药的患者相比是否有更好或更差的结果。由于许多抗抑郁药的功能是多巴胺激动剂和拮抗剂，如果多巴胺是一种真正的肿瘤抑制剂，这项研究可能会对这类药物重新定位癌症治疗产生影响。