Regulation of Tumor and Metastatic Growth by Hypoxia and CTGF

缺氧和 CTGF 对肿瘤和转移性生长的调节

基本信息

  • 批准号:
    8208641
  • 负责人:
  • 金额:
    $ 25.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-02-01 至 2013-01-31
  • 项目状态:
    已结题

项目摘要

During the last grant period, we have obtained evidence that the expression of connective tissue growth factor (CTGF) is elevated in human pancreatic tumors, but not in normal pancreas or pancreatitis. Since pancreatic tumors are highly hypoxia and CTGF is known to be hypoxia inducible, we have focused this grant to understand the role of hypoxia and CTGF in pancreatic tumor progression. The basis for these studies to investigate the importance of CTGF in pancreatic tumor progression derive from our demonstration that targeted inhibition of CTGF with a monoclonal specific antibody results in significant growth inhibition of two different pancreatic cancer cell lines implanted as subcutaneous tumors. In this competitive renewal, Project 1 will focus on determining the mechanistic role of CTGF and its individual domains on pancreatic tumor progression under normoxic and hypoxic conditions. Our preliminary data suggests that CTGF is able to enhance the growth of pancreatic tumor cells. Induction of CTGF had no effect on cell growth on plastic, but significantly enhanced spheroid growth in soft agar. Most striking was the increase in cell adhesion induced by CTGF expression. These changes in cell adhesion that are necessary for 3-D growth lead us to test the hypothesis that one of the major roles of CTGF in malignant progression is to regulate cell-cell adhesion, and that inhibiting this activity will impact tumor growth and metastases. Thus, the aims of this proposal are to 1) determine how CTGF affects cell adhesion of pancreatic tumor cells under normoxic and hypoxic conditions using domain specific deletion mutants in cells that are manipulated to express different levels of HIF-1 (Project 3), 2) determine how important CTGF is for 3-D growth and invasion under normoxic and hypoxic conditions, 3) determine how inhibition of CTGF mediated adhesion affects metastatic growth, 4) determine how inhibition of cell adhesion by CTGF affects subcutaneous and orthotopic tumor growth of pancreatic tumor cells and in collaboration with Project 4 head and neck tumors, 5) determine the role of stromal and tumor cell CTGF on tumor growth, 6) determine how effective the combination of CTGF Ab and the new hypoxic specific cytotoxin PR-104 are in controlling pancreatic tumor growth compared to CTGF Ab and gemcitabine (Project 2). In summary, the proposed studies are intended to address an important mechanism by which CTGF affects tumor progression in pancreatic cancers and to determine how effective it is in combination therapy to bring it to the clinic.
在上一个资助期间,我们获得了结缔组织生长表达的证据

项目成果

期刊论文数量(0)
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专利数量(0)

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Amato J. Giaccia其他文献

Benzamides substitués et leurs utilisations
苯甲酰胺替代品和用途
  • DOI:
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    0
  • 作者:
    M. Bonnet;Denise A. Chan;Amato J. Giaccia;Michael Patrick Hay;Edwin W. Lai;Olga V. Razorenova;Connie Sun;Ray Tabibiazar;Po
  • 通讯作者:
    Po
88: Lysyl Oxidase Is Essential for Hypoxia-Induced Metastasis
  • DOI:
    10.1016/j.ijrobp.2006.07.118
  • 发表时间:
    2006-11-01
  • 期刊:
  • 影响因子:
  • 作者:
    Janine Erler;Quynh Le;Amato J. Giaccia
  • 通讯作者:
    Amato J. Giaccia
Lysyl oxidase is essential for hypoxia-induced metastasis
赖氨酰氧化酶对于缺氧诱导的转移是必不可少的
  • DOI:
    10.1038/nature04695
  • 发表时间:
    2006-04-27
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Janine T. Erler;Kevin L. Bennewith;Monica Nicolau;Nadja Dornhöfer;Christina Kong;Quynh-Thu Le;Jen-Tsan Ashley Chi;Stefanie S. Jeffrey;Amato J. Giaccia
  • 通讯作者:
    Amato J. Giaccia
Hypoxic gene expression and metastasis
  • DOI:
    10.1023/b:canc.0000031768.89246.d7
  • 发表时间:
    2004-08-01
  • 期刊:
  • 影响因子:
    8.700
  • 作者:
    Quynh-Thu Le;Nicholas C. Denko;Amato J. Giaccia
  • 通讯作者:
    Amato J. Giaccia
Therapeutic targeting of the functionally elusive TAM receptor family
对功能上难以捉摸的 TAM 受体家族的治疗靶向
  • DOI:
    10.1038/s41573-023-00846-8
  • 发表时间:
    2023-12-13
  • 期刊:
  • 影响因子:
    101.800
  • 作者:
    Yu Rebecca Miao;Erinn B. Rankin;Amato J. Giaccia
  • 通讯作者:
    Amato J. Giaccia

Amato J. Giaccia的其他文献

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{{ truncateString('Amato J. Giaccia', 18)}}的其他基金

Project 1: Inhibition of Complement C5aR1 Radioprotects Normal Tissue and Radiosensitizes Tumors
项目 1:抑制补体 C5aR1 辐射保护正常组织并使肿瘤辐射增敏
  • 批准号:
    10707880
  • 财政年份:
    2022
  • 资助金额:
    $ 25.35万
  • 项目类别:
Project 1: Inhibition of Complement C5aR1 Radioprotects Normal Tissue and Radiosensitizes Tumors
项目 1:抑制补体 C5aR1 辐射保护正常组织并使肿瘤辐射增敏
  • 批准号:
    10334199
  • 财政年份:
    2022
  • 资助金额:
    $ 25.35万
  • 项目类别:
Preclinical Testing of a Novel Therapy Targeting AXL in Advanced Kidney Cancer
针对晚期肾癌 AXL 的新疗法的临床前测试
  • 批准号:
    8949353
  • 财政年份:
    2016
  • 资助金额:
    $ 25.35万
  • 项目类别:
The Impact of Mitochondrial Repression and Lipid Accumulation by HIF on Tumor Growth
HIF 抑制线粒体和脂质积累对肿瘤生长的影响
  • 批准号:
    10212325
  • 财政年份:
    2015
  • 资助金额:
    $ 25.35万
  • 项目类别:
The Impact of Mitochondrial Repression and Lipid Accumulation by HIF on Tumor Growth
HIF 抑制线粒体和脂质积累对肿瘤生长的影响
  • 批准号:
    9976465
  • 财政年份:
    2015
  • 资助金额:
    $ 25.35万
  • 项目类别:
HIF-1alpha, a Survival and Differentiation Factor for Cartilage
HIF-1alpha,软骨的存活和分化因子
  • 批准号:
    8609400
  • 财政年份:
    2013
  • 资助金额:
    $ 25.35万
  • 项目类别:
Administration & Scientific Support
行政
  • 批准号:
    8208647
  • 财政年份:
    2011
  • 资助金额:
    $ 25.35万
  • 项目类别:
Regulation of Tumor and Metastatic Growth by Hypoxia and CTGF
缺氧和 CTGF 对肿瘤和转移性生长的调节
  • 批准号:
    8492949
  • 财政年份:
    2011
  • 资助金额:
    $ 25.35万
  • 项目类别:
Radiation Biology
放射生物学
  • 批准号:
    8180970
  • 财政年份:
    2010
  • 资助金额:
    $ 25.35万
  • 项目类别:
Postdoctoral Training in the Radiation Sciences
放射科学博士后培训
  • 批准号:
    7233332
  • 财政年份:
    2007
  • 资助金额:
    $ 25.35万
  • 项目类别:

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