# Regulation of primary metastasis in high grade serous ovarian cancer

> **NIH NIH F30** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $53,974

## Abstract

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.

## Key facts

- **NIH application ID:** 10845282
- **Project number:** 5F30CA260791-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Tova Bergsten
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2021-05-16 → 2025-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10845282

## Citation

> US National Institutes of Health, RePORTER application 10845282, Regulation of primary metastasis in high grade serous ovarian cancer (5F30CA260791-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10845282. Licensed CC0.

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