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Regulation of primary metastasis in high grade serous ovarian cancer

高级别浆液性卵巢癌原发转移的调节

基本信息

批准号：
10608098
负责人：
Tova Bergsten
金额：
$ 5.27万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-16 至 2025-05-15
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10608098
关键词：
Address Adrenergic Agents Adrenergic beta-Antagonists Adverse effects Anabolism Automobile Driving CRISPR/Cas technology Cancer Biology Cancer Patient Cells Chemicals Chemoprevention Clinical Clinical Management Coculture Techniques Communication Cues Data Development Diagnosis Disease Disease Progression Distant Metastasis Early Intervention Epithelial Cells Epithelium Event FDA approved Goals Human Immunotherapy Invaded Lesion Malignant - descriptor Malignant Neoplasms Malignant neoplasm of ovary Mammalian Oviducts Mediator Molecular Mus Mutation Neoplasm Metastasis Norepinephrine Osteonectin Outcome Ovarian Ovary PI3K/AKT Pathway interactions Patient Care Patients Peritoneal Pharmaceutical Preparations Physicians Production Prognosis Propranolol Radiation therapy Refractory Regulation Rest Role Scientist Series Serous Signal Transduction Soil Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization System TP53 gene Techniques Testing Time Training Translating Tumor Promoters Tumor Suppressor Proteins Up-Regulation Woman Xenograft procedure advanced disease antagonist beta-2 Adrenergic Receptors beta-adrenergic receptor clinical practice cost drug repurposing expectation experimental study high risk improved improved outcome inhibitor insight malignant phenotype mass spectrometric imaging migration neoplastic cell novel strategies ovarian neoplasm overexpression paracrine pharmacologic precision medicine prevent receptor release factor response small hairpin RNA standard of care tumor tumor progression tumorigenic

项目摘要

Project Summary/Abstract High grade serous ovarian cancer (HGSOC) is both the most common and most lethal ovarian cancer histotype. Though HGSOC has been long thought to originate in the ovary, recent evidence now suggests that HGSOC precursor lesions in fact originate in the fallopian tube. Further, select dysplastic cells from the fallopian tube disseminate from these precursor lesions and follow a variety of local migratory cues in order to colonize the ovary and establish a primary HGSOC tumor. The ovary seems to facilitate the expansion and spread of the ovary to the rest of the peritoneal space. Though this phenomenon is well documented, the molecular mechanisms that drive the initial dissemination of dysplastic fallopian tube cells to the ovary are poorly understood. To address this, our group has developed a new imaging mass spectrometry technique that has allowed for unprecedented insight into the paracrine factors that create a pro-metastatic niche and allow for the migration of fallopian tube cells toward the ovary. Using this technique, we determined that co-culture of murine ovary explants with dysplastic tubal cells leads to consistent increases in norepinephrine secretion from the ovary, later found to be produced by the ovary itself. This is significant, as norepinephrine is an established tumor promoter in advanced disease, and ovarian cancer patients taking β-blockers that interfere with norepinephrine signals typically have improved clinical outcomes. However, the role of norepinephrine in tumor development is largely unknown. Given the wide availability, low cost, and minimal adverse effects of β- blockers, should norepinephrine similarly enhance the development of HGSOC this may provide opportunity for early intervention and/or chemoprevention in high-risk patients. Given the potential to directly impact clinical practice, it is essential to further dissect both the mechanisms that direct norepinephrine biosynthesis, as well as the downstream effects of norepinephrine during HGSOC development. Through the experiments detailed in this proposal, we will gain valuable insight into these events in hopes of either preventing or delaying HGSOC development in high-risk patients.

项目总结/文摘

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）

Fallopian tube secreted protein affects ovarian metabolites in high grade serous ovarian cancer.

DOI：
10.3389/fcell.2022.1042734
发表时间：
2022
期刊：
Frontiers in cell and developmental biology
影响因子：
5.5
作者：
通讯作者：

Home-Built Spinning Apparatus for Drying Agarose-Based Imaging Mass Spectrometry Samples.

DOI：
10.1021/jasms.2c00044
发表时间：
2022-07-06
期刊：
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
影响因子：
3.2
作者：
Lusk, Hannah J.;Levy, Sarah E.;Bergsten, Tova M.;Burdette, Joanna E.;Sanchez, Laura M.
通讯作者：
Sanchez, Laura M.

Kaempferol, a Phytoprogestin, Induces a Subset of Progesterone-Regulated Genes in the Uterus.