# Ovarian Epithelial Cancer Progenitor Cell Population

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $157,823

## Abstract

Project Summary
This research project is to study a putative ovarian cancer progenitor and stem cell population, and the impact
of menopause on the potential for the cells to undergo transformation. We have made a surprising discovery
that a mosaic subpopulation of ovarian and fallopian tube epithelial cells is derived from MISR2 (Mullerian
inhibitory substance receptor type 2) lineage. Furthermore, these cells of MISR2-derived subpopulation have
high proliferative potential and develop epithelial tumors in mice that ovarian follicles are depleted. Based on
our recent studies (published and unpublished), we have developed a unique hypothesis that the MISR2-derived
subpopulation of ovarian and fallopian tube epithelial cells are epithelial stem cells and precursors of ovarian
cancer. Additionally, these cells are responsive to suppression by MIS/AMH (Mullerian inhibitory substance/anti-
Mullerian hormone) produced by granulosa cells of ovarian follicles. We plan to test these ideas by studying the
MISR2-containing ovarian and fallopian tube epithelial cells for their growth and stem cell properties, and also
study their response to the MIS factor, in both mouse models and human cells and tissues. Previously, we found
that ovarian follicles and granulosa cells produce a growth inhibitory factor(s) towards ovarian epithelial cells in
culture, and provided evidence that MIS is a strong candidate for the factor. We will seek to identify the factor(s)
produced by granulosa cells using a transwell device for co-culturing of ovarian and fallopian tube epithelial cells
with granulosa cells, and to verify if MIS contributes to part or all of the inhibitory activity. Experiments designed
are also to test the roles of the MIS/MISR2 paracrine/endocrine pathway in maintaining the tissues homeostasis
of the ovarian and fallopian tube environment, and in tumor suppression, as summarized in two main aims. The
first major aim is to characterize the MISR2-positive cells to determine if these cells are progenitor/stem cell like,
and precursors for ovarian cancer. The second major aim is to identify the tumor suppressing factor(s) produced
by follicles/granulosa cells and to study its regulation of ovarian epithelial cells in ovarian tissue homeostasis.
Granulosa cell-derived MIS will be tested as a strong candidate of the follicle-derived factor. The experiments
will use human ovarian cancer tissues, primary and established cells, and transgenic mutant mouse models to
study molecular mechanisms and relevance to human ovarian tissue and cancer. The findings and conclusions
from the study of cell and mouse models will be verified in human normal and cancer tissues. If successful, our
work will solve the long-standing puzzle for the reason why ovarian cancer risk is high in menopausal women.
The research will also gain insight into an ovarian epithelial and cancer stem cell population, and will yield a
substantial new advance in ovarian cancer biology.

## Key facts

- **NIH application ID:** 10060282
- **Project number:** 3R01CA230916-03S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** XiangXi Mike Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $157,823
- **Award type:** 3
- **Project period:** 2018-05-10 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10060282

## Citation

> US National Institutes of Health, RePORTER application 10060282, Ovarian Epithelial Cancer Progenitor Cell Population (3R01CA230916-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10060282. Licensed CC0.

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