# Dynamic Interactions of the Ovarian-Fallopian Axis in High Grade Serous Ovarian Cancer

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $538,941

## Abstract

Ovarian cancer is the most lethal cancer of the female reproductive system, with over 21,000 new ovarian
cancer diagnoses and 14,000 deaths annually in the US. The menstrual cycle, specifically the total lifetime
number of ovulations, is a key risk factor for developing ovarian cancer. Factors that repress ovulation reduce
the risk of ovarian cancer, such as oral contraceptives, pregnancy, and late menarche. The most common and
deadly histotype of ovarian cancer, termed high grade serous cancer (HGSC), likely originates from the
fallopian tube epithelial cells, and not the ovary. The frequent detection of tumors in the ovary, which resulted
in the name “ovarian cancer”, suggests that the ovary provides a unique anatomical location for tumor
migration and expansion. Since most research supports that the fallopian tube is the source of ovarian cancer,
it becomes critical to understand how ovulation contributes to tumor initiation in this site. Our team developed
three-dimensional organotypic cultures supported in a state-of-the-art microfluidic platform that supports the
ovary to produce dynamic hormone profiles that closely mimic the 28-day human reproductive menstrual cycle
and ovulation on platform. The device was one of the C&E News Top 10 Inventions of 2017 and our paper in
Nature Communications was the top NIEHS paper of 2017. The proposal will build on this successful
collaboration to expand our technology and models to studying the role of the ovary in fallopian tube
carcinogenesis and metastasis. Our hypothesis is that the microenvironment of the ovary contributes to
tumor initiation, migration, and tumor cell expansion of high grade serous cancers derived from
fallopian tube. Aim 1 will integrate our 3D culture of the ovary and models of the fallopian tube in a new
PREDICT96 microfluidic device to define the how the physiological process of ovulation, specifically follicular
fluid, drives fallopian tube tumor initiation using primary human fallopian tube samples, preneoplastic cell
models, tumor models, and a transgenic mouse model developed in the Burdette lab. In Aim 2, we will validate
the role of the secreted protein, versican, from the 3D ovary that enhances fallopian tube homing to the ovary
and we will test small molecules for their ability to block ovarian colonization using 3D ex vivo microfluidic
models and in vivo. In Aim 3, we will investigate the mechanisms responsible for tumor cell escape from the
fallopian tube, which we hypothesize is due to spheroid formation and the colonization of exposed three-
dimensional collagen in the ovary at sites of ovulation. Overall, this grant will employ unique devices, primary
human tissues, and three dimensional preneoplastic and tumor models to unveil new biological targets in an
effort to reduce tumor initiation and spread of fallopian derived high grade serous cancer in the ovarian
microenvironment.

## Key facts

- **NIH application ID:** 9969356
- **Project number:** 5R01CA240301-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Joanna E Burdette
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $538,941
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969356

## Citation

> US National Institutes of Health, RePORTER application 9969356, Dynamic Interactions of the Ovarian-Fallopian Axis in High Grade Serous Ovarian Cancer (5R01CA240301-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9969356. Licensed CC0.

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