# Ovarian Epithelial Cancer Progenitor Cell Population

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $556,445

## Abstract

ABSTRACT
 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 Based on our recent studies (published and unpublished), we have developed a unique hypothesis that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:** 10142382
- **Project number:** 5R01CA230916-04
- **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:** 2021
- **Award amount:** $556,445
- **Award type:** 5
- **Project period:** 2018-05-10 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142382

## Citation

> US National Institutes of Health, RePORTER application 10142382, Ovarian Epithelial Cancer Progenitor Cell Population (5R01CA230916-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10142382. Licensed CC0.

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