"Neutrophil Elastase Links Idiopathic Pulmonary Fibrosis and Lung Cancer"

“中性粒细胞弹性蛋白酶与特发性肺纤维化和肺癌有关”

基本信息

项目摘要

DESCRIPTION (provided by applicant): Lung cancer and idiopathic pulmonary fibrosis (IPF) are linked diseases, with IPF patients being at a seven-fold increased risk of lung cancer. Both of these diseases can be characterized by dismal patient outcomes and the lack of effective disease modifying therapies. The identification of common disease progressing substances may yield novel therapeutic targets. We propose that the neutrophil-derived serine proteinase, neutrophil elastase (NE), is such a target. NE drives disease progression of both lung adenocarcinoma and lung fibrosis in mouse models via similar mechanisms. NE impacts the target cell in cancer and fibrosis, the tumor cell and fibroblast, respectively, in two distinct ways. First, NE induces tumor cell and fibroblast proliferation. Second, NE alters the behavior of tumor cells and fibroblasts, generating tumor cell epithelial to mesenchymal transition (EMT), and driving myofibroblast differentiation. Both of these processes are intimately linked to advanced disease in the setting of lung cancer and IPF. This proposal will identify the mechanisms by which NE induces cell proliferation and alters cell behavior in hopes to identify novel therapeutic targets common to both diseases. Additionally, these studies should validate NE itself, as a valid therapeutic target for patients inflicted with lung cancer and/or IPF.
描述(申请人提供):肺癌和特发性肺纤维化(IPF)是相互关联的疾病,IPF患者患肺癌的风险增加七倍。这两种疾病的特点都是患者结局惨淡,缺乏有效的疾病修正疗法。常见疾病进展物质的鉴定可能产生新的治疗靶点。我们认为中性粒细胞衍生的丝氨酸蛋白酶,中性粒细胞弹性蛋白酶(NE)就是这样的靶点。在小鼠模型中,NE通过类似的机制推动肺腺癌和肺纤维化的疾病进展。NE分别以两种不同的方式影响癌症和纤维化中的靶细胞,即肿瘤细胞和成纤维细胞。首先,去甲肾上腺素可诱导肿瘤细胞和成纤维细胞增殖。其次,去甲肾上腺素改变肿瘤细胞和成纤维细胞的行为,产生肿瘤细胞上皮向间充质转化(EMT),并驱动肌成纤维细胞的分化。这两个过程都与肺癌和IPF的晚期疾病密切相关。这项建议将确定NE诱导细胞增殖和改变细胞行为的机制,希望确定这两种疾病共同的新治疗靶点。此外,这些研究应该验证NE本身作为肺癌和/或IPF患者的有效治疗靶点。

项目成果

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A McGarry Houghton其他文献

A McGarry Houghton的其他文献

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{{ truncateString('A McGarry Houghton', 18)}}的其他基金

Neutrophil derived proteinases abolish the IFNG signature in NSCLC
中性粒细胞衍生的蛋白酶消除 NSCLC 中的 IFNG 特征
  • 批准号:
    10717448
  • 财政年份:
    2023
  • 资助金额:
    $ 40.8万
  • 项目类别:
Anxa2 drives the function of immune suppressive neutrophils in lung cancer
Anxa2 驱动肺癌中免疫抑制性中性粒细胞的功能
  • 批准号:
    10310981
  • 财政年份:
    2021
  • 资助金额:
    $ 40.8万
  • 项目类别:
A Quantitative PET/CT Research Resource for Co-Clinical Imaging of Lung Cancer Therapies
用于肺癌治疗联合临床成像的定量 PET/CT 研究资源
  • 批准号:
    10301566
  • 财政年份:
    2021
  • 资助金额:
    $ 40.8万
  • 项目类别:
A Quantitative PET/CT Research Resource for Co-Clinical Imaging of Lung Cancer Therapies
用于肺癌治疗联合临床成像的定量 PET/CT 研究资源
  • 批准号:
    10700944
  • 财政年份:
    2021
  • 资助金额:
    $ 40.8万
  • 项目类别:
Liquid biopsy of the lung to profile lung cancer
肺部液体活检以分析肺癌
  • 批准号:
    10053675
  • 财政年份:
    2020
  • 资助金额:
    $ 40.8万
  • 项目类别:
Liquid biopsy of the lung to profile lung cancer
肺部液体活检以分析肺癌
  • 批准号:
    10259860
  • 财政年份:
    2020
  • 资助金额:
    $ 40.8万
  • 项目类别:
Liquid biopsy of the lung to profile lung cancer
肺部液体活检以分析肺癌
  • 批准号:
    10472743
  • 财政年份:
    2020
  • 资助金额:
    $ 40.8万
  • 项目类别:
Liquid biopsy of the lung to profile lung cancer
肺部液体活检以分析肺癌
  • 批准号:
    10601449
  • 财政年份:
    2020
  • 资助金额:
    $ 40.8万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10174875
  • 财政年份:
    2019
  • 资助金额:
    $ 40.8万
  • 项目类别:
Project 1: Targeting the Neutrophil Lineage To Enhance Immune Checkpoint Inhibitor Efficacy in NSCLC
项目1:靶向中性粒细胞谱系以增强非小细胞肺癌中免疫检查点抑制剂的功效
  • 批准号:
    10174872
  • 财政年份:
    2019
  • 资助金额:
    $ 40.8万
  • 项目类别:

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