Beige Adipocytes and African American Breast Tumors

米色脂肪细胞和非裔美国人乳腺肿瘤

基本信息

  • 批准号:
    10202503
  • 负责人:
  • 金额:
    $ 35.88万
  • 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:
    2018-07-06 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

African American (AA) women continue to suffer from high mortality rates from an aggressive form of breast cancer for which there is no treatment. Better understanding of the unique properties of AA tumor cells and the microenvironment that supports its growth might improve clinical outcomes. Macrophages are a lynchpin in tumor microenvironment regulation. Although high macrophage infiltration and increased angiogenesis are unique characteristics of AA breast tumors, mechanisms that support these biological processes remain poorly understood. We have recently demonstrated, for the first time that increase in beige/brown adipose phenotype promote development of xenografts from breast cancer cells. We have subsequently demonstrated that expression of beige markers is significantly increased in both xenografts obtained from AA triple- negative (TN) breast cancer cells as well as in AA TN breast tumors. Based on our published and preliminary data, we hypothesize that “cross-talk between tumor cells and beige adipocytes generates a unique microenvironment that promotes M2 macrophage phenotype and is conducive to high angiogenesis.” We will test our hypothesis with the following Specific Aims: Aim 1: Determine whether i) M2 macrophages increase beige adipose phenotype in breast cancer cells and ii) beige adipose cells crosstalk with tumor cells to increase aggressive behavior in AA TN breast tumors. Aim 2: Determine the molecular mechanisms by which beige adipocytes in AA breast tumors support and sustain M2 macrophage population. Aim 3: Determine whether Th2 cytokines in AA TN breast tumor microenvironment promote proliferation and commitment of bi-potent adipose precursors (AP) to beige lineage. Effect of depletion of tissue resident macrophages and tyrosine hydroxylase (TH) expressed in these macrophages, on beige adipose phenotype as well as tumor growth in-vivo will be analyzed. Co-culture experiments with adipocytes enriched in beige phenotype and AA TN breast cancer cells will be performed to elucidate mechanisms that support M2 macrophages/angiogenesis. We will examine the possible role of psoriasin, and beige adipose-enriched secretory factors Neuregulin 4 (Nrg4) and Meteorin- like (Metrnl) during the cross-talk between cancer cells and beige adipocytes. We will further analyze the role of psoriasin in promoting MCSC (ALDH+)-induced xenograft growth. Depletion/enrichment of breast tumor cells with adipose precursor PDGFRα cells will be examined for tumor growth, beige adipose/M2 markers and tumor growth. Increased understanding of detailed molecular mechanisms by which beige adipocytes sustain critical threshold of M2 macrophage population in tumor microenvironment and contribute to tumor progression may provide outstanding opportunity for therapeutic intervention for these aggressive AA TN breast tumors.
非裔美国人(AA)妇女因性侵而继续遭受高死亡率

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
DUSP9-mediated reduction of pERK1/2 supports cancer stem cell-like traits and promotes triple negative breast cancer.
  • DOI:
  • 发表时间:
    2020-10
  • 期刊:
  • 影响因子:
    5.3
  • 作者:
    Thalia Jimenez;Albert Barrios;A. Tucker;Javier Collazo;Nataly Arias;S. Fazel;Melanie Baker;M. Halim;T. Huynh;R. Singh;S. Pervin
  • 通讯作者:
    Thalia Jimenez;Albert Barrios;A. Tucker;Javier Collazo;Nataly Arias;S. Fazel;Melanie Baker;M. Halim;T. Huynh;R. Singh;S. Pervin
Nicotine Synergizes with High-Fat Diet to Induce an Anti-Inflammatory Microenvironment to Promote Breast Tumor Growth.
  • DOI:
    10.1155/2020/5239419
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Jimenez T;Friedman T;Vadgama J;Singh V;Tucker A;Collazo J;Sinha S;Hikim AS;Singh R;Pervin S
  • 通讯作者:
    Pervin S
Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues.
  • DOI:
    10.3390/cells10113030
  • 发表时间:
    2021-11-05
  • 期刊:
  • 影响因子:
    6
  • 作者:
    Singh R;Barrios A;Dirakvand G;Pervin S
  • 通讯作者:
    Pervin S
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

SHEHLA PERVIN其他文献

SHEHLA PERVIN的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('SHEHLA PERVIN', 18)}}的其他基金

Electronic cigarettes, oxidative stress and development of breast tumor
电子烟、氧化应激与乳腺肿瘤的发生
  • 批准号:
    10629814
  • 财政年份:
    2023
  • 资助金额:
    $ 35.88万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8078639
  • 财政年份:
    2011
  • 资助金额:
    $ 35.88万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8677817
  • 财政年份:
    2011
  • 资助金额:
    $ 35.88万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8881968
  • 财政年份:
    2011
  • 资助金额:
    $ 35.88万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8299474
  • 财政年份:
    2011
  • 资助金额:
    $ 35.88万
  • 项目类别:
Targeting pERK1/2 in Human Mammary Cancer Stem Cells
靶向人类乳腺癌干细胞中的 pERK1/2
  • 批准号:
    8509637
  • 财政年份:
    2011
  • 资助金额:
    $ 35.88万
  • 项目类别:
Drew National High School Student Summer Research Apprentice Program
德鲁国家高中生暑期研究学徒计划
  • 批准号:
    9024513
  • 财政年份:
    2007
  • 资助金额:
    $ 35.88万
  • 项目类别:
p38 MAP Kinase and Akt Interaction in HUVEC
HUVEC 中 p38 MAP 激酶和 Akt 相互作用
  • 批准号:
    7253731
  • 财政年份:
    2007
  • 资助金额:
    $ 35.88万
  • 项目类别:

相似海外基金

Deciphering the role of adipose tissue in common metabolic disease via adipose tissue proteomics
通过脂肪组织蛋白质组学解读脂肪组织在常见代谢疾病中的作用
  • 批准号:
    MR/Y013891/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.88万
  • 项目类别:
    Research Grant
ESTABLISHING THE ROLE OF ADIPOSE TISSUE INFLAMMATION IN THE REGULATION OF MUSCLE MASS IN OLDER PEOPLE
确定脂肪组织炎症在老年人肌肉质量调节中的作用
  • 批准号:
    BB/Y006542/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.88万
  • 项目类别:
    Research Grant
Activation of human brown adipose tissue using food ingredients that enhance the bioavailability of nitric oxide
使用增强一氧化氮生物利用度的食品成分激活人体棕色脂肪组织
  • 批准号:
    23H03323
  • 财政年份:
    2023
  • 资助金额:
    $ 35.88万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of new lung regeneration therapies by elucidating the lung regeneration mechanism of adipose tissue-derived stem cells
通过阐明脂肪组织干细胞的肺再生机制开发新的肺再生疗法
  • 批准号:
    23K08293
  • 财政年份:
    2023
  • 资助金额:
    $ 35.88万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Canadian Alliance of Healthy Hearts and Minds: Dissecting the Pathways Linking Ectopic Adipose Tissue to Cognitive Dysfunction
加拿大健康心灵联盟:剖析异位脂肪组织与认知功能障碍之间的联系途径
  • 批准号:
    479570
  • 财政年份:
    2023
  • 资助金额:
    $ 35.88万
  • 项目类别:
    Operating Grants
Determinants of Longitudinal Progression of Adipose Tissue Inflammation in Individuals at High-Risk for Type 2 Diabetes: Novel Insights from Metabolomic Profiling
2 型糖尿病高危个体脂肪组织炎症纵向进展的决定因素:代谢组学分析的新见解
  • 批准号:
    488898
  • 财政年份:
    2023
  • 资助金额:
    $ 35.88万
  • 项目类别:
    Operating Grants
A study on the role of brown adipose tissue in the development and maintenance of skeletal muscles
棕色脂肪组织在骨骼肌发育和维持中作用的研究
  • 批准号:
    23K19922
  • 财政年份:
    2023
  • 资助金额:
    $ 35.88万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
A mechanism of lipid accumulation in brown adipose tissue
棕色脂肪组织中脂质积累的机制
  • 批准号:
    10605981
  • 财政年份:
    2023
  • 资助金额:
    $ 35.88万
  • 项目类别:
Obesity and Childhood Asthma: The Role of Adipose Tissue
肥胖和儿童哮喘:脂肪组织的作用
  • 批准号:
    10813753
  • 财政年份:
    2023
  • 资助金额:
    $ 35.88万
  • 项目类别:
Estrogen Signaling in the Ventromedial Hypothalamus Modulates Adipose Tissue Metabolic Adaptation
下丘脑腹内侧区的雌激素信号调节脂肪组织代谢适应
  • 批准号:
    10604611
  • 财政年份:
    2023
  • 资助金额:
    $ 35.88万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了