Pre-metastatic Omental Niche Formation in Ovarian Cancer

卵巢癌转移前网膜微环境的形成

基本信息

  • 批准号:
    10360586
  • 负责人:
  • 金额:
    $ 35.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-04-01 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

Bowel obstruction is a leading cause of death in women with ovarian cancer and often stems from growth of tumors on the omentum, a fat pad that suspends from the stomach. The objective of this project is to determine the mechanisms that cause ovarian cancer cells to implant on the omentum, with the overarching goal of identifying more effective therapies for this lethal disease. Previous studies of ovarian cancer metastasis have mostly focused on investigating interactions of cancer cells with adipocytes, macrophages, fibroblasts and mesothelial cells. However, as these stromal cells are constituents of all visceral fat pads, interactions with these cells may not fully explain the tropism of ovarian cancer cells for the omentum. Neutrophils act as the first line of defense in response to infection or malignancy. Because the omentum is the major site of neutrophil influx into the peritoneal cavity, we speculate that neutrophils direct ovarian cancer cells to the omental niche. This study focuses on a phenomenon in which neutrophils extrude sticky DNA webs called neutrophil extracellular traps (NETs). NETs were originally discovered to trap microbes in infectious diseases but very little is known about the significance of NETs in cancer. Based on our preliminary studies, we hypothesize that ovarian cancer cells induce neutrophils to form NETs in the omentum, and that omental metastasis stems in part from entrapment of cancer cells by NETs in the omental niche. In this project, we will determine whether (1) ovarian cancers induce NET formation in the pre-metastatic omental niche, (2) omental metastasis of ovarian cancer depends on NET formation and (3) omental metastasis is decreased by treatment with agents that inhibit NETs. These aims will be accomplished by evaluating patient clinical specimens, mouse tumor models and genetically modified mice that are defective in NET formation. Our study will provide new and provocative insights into the mechanisms that drive the propensity of ovarian cancer to colonize the omentum and the potential of repurposing NET-inhibiting agents for ovarian cancer therapy.
肠梗阻是卵巢癌女性患者死亡的主要原因,通常源于肿瘤的生长

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The glycoprotein CD147 defines miRNA-enriched extracellular vesicles that derive from cancer cells.
Normal saline remodels the omentum and stimulates its receptivity for transcoelomic metastasis.
  • DOI:
    10.1172/jci.insight.167336
  • 发表时间:
    2023-06-22
  • 期刊:
  • 影响因子:
    8
  • 作者:
    Akasaka, Hironari;Lee, WonJae;Ko, Song Yi;Lengyel, Ernst;Naora, Honami
  • 通讯作者:
    Naora, Honami
Revisiting the Use of Normal Saline for Peritoneal Washing in Ovarian Cancer.
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Honami Naora其他文献

Honami Naora的其他文献

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{{ truncateString('Honami Naora', 18)}}的其他基金

Boosting anti-tumor immunity in the omentum for metastasis prevention
增强大网膜的抗肿瘤免疫力以预防转移
  • 批准号:
    10648192
  • 财政年份:
    2023
  • 资助金额:
    $ 35.35万
  • 项目类别:
Isolation of miRNA-rich extracellular vesicles for liquid biopsy
分离富含 miRNA 的细胞外囊泡用于液体活检
  • 批准号:
    10579299
  • 财政年份:
    2022
  • 资助金额:
    $ 35.35万
  • 项目类别:
Isolation of miRNA-rich extracellular vesicles for liquid biopsy
分离富含 miRNA 的细胞外囊泡用于液体活检
  • 批准号:
    10431224
  • 财政年份:
    2022
  • 资助金额:
    $ 35.35万
  • 项目类别:
Impact of diagnostic peritoneal lavage on omentum metastasis
诊断性腹腔灌洗对大网膜转移的影响
  • 批准号:
    10286303
  • 财政年份:
    2021
  • 资助金额:
    $ 35.35万
  • 项目类别:
Impact of diagnostic peritoneal lavage on omentum metastasis
诊断性腹腔灌洗对大网膜转移的影响
  • 批准号:
    10447751
  • 财政年份:
    2021
  • 资助金额:
    $ 35.35万
  • 项目类别:
Pre-metastatic Omental Niche Formation in Ovarian Cancer
卵巢癌转移前网膜微环境的形成
  • 批准号:
    10117199
  • 财政年份:
    2018
  • 资助金额:
    $ 35.35万
  • 项目类别:
Pre-metastatic Omental Niche Formation in Ovarian Cancer
卵巢癌转移前网膜微环境的形成
  • 批准号:
    9903259
  • 财政年份:
    2018
  • 资助金额:
    $ 35.35万
  • 项目类别:
Mechanism of evasion by ovarian cancers from anti-VEGF therapy
卵巢癌逃避抗 VEGF 治疗的机制
  • 批准号:
    9302312
  • 财政年份:
    2016
  • 资助金额:
    $ 35.35万
  • 项目类别:
Mechanism of evasion by ovarian cancers from anti-VEGF therapy
卵巢癌逃避抗 VEGF 治疗的机制
  • 批准号:
    9152040
  • 财政年份:
    2016
  • 资助金额:
    $ 35.35万
  • 项目类别:
Stromal Interactions and Leukemic Risk in Myelodysplastic Syndromes
骨髓增生异常综合征中的基质相互作用和白血病风险
  • 批准号:
    8897103
  • 财政年份:
    2015
  • 资助金额:
    $ 35.35万
  • 项目类别:

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