# Mechanisms Underlying the Omental Support of Ovarian Cancer Peritoneal Metastasis

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2024 · $53,974

## Abstract

PROJECT SUMMARY
More than 80% of ovarian cancer (OC) cases have already metastasized to the peritoneal cavity at diagnosis,
and the five-year survival for these patients is 25%. Within the peritoneal cavity, the most common site of
metastasis is the omentum, a well-vascularized, specialized adipose tissue that arises off the greater curvature
of the stomach. Because the omentum promotes tumor growth, it is removed as a standard of care for patients
with peritoneal metastases. In mouse OC models, the omentum is an early metastatic site, and removing the
omentum before tumor implantation reduces the pace of tumor expansion. Once OC cells shed from the
primary tumor and form spheroids, some bind to the adjacent omentum, which is considered transcoelomic
metastasis. Other data show that OC cells can exit the peritoneal cavity and travel back to the omentum via the
circulatory system, underscoring a hematogenous peritoneal metastatic pathway. Overall, the mechanism by
which the omentum promotes tumor growth is still unknown and is important to identify so that we can develop
more specific therapeutic strategies. Studies suggest that omental macrophages, blood vessels, or lymphoid
aggregates called milky spots, are key features that support tumor growth. In addition to these omental
features, the adipocytes themselves, the cells that define the omentum as a fat pad, are likely important for
tumor expansion. Adipocytes can directly provide fatty acids to metabolically support tumor proliferation or may
indirectly foster tumor growth by supporting milky spot formation, as my preliminary data suggest. To move
beyond these valuable observational studies, I herein propose using a mouse model wherein the mouse lacks
white and brown adipocytes, rendering the peritoneal cavity adipocyte-free, to explore the role of the omentum
in OC metastasis without mature adipocytes. Due to a total lack of fat, the mice become lipodystrophic. To
overcome this systemic metabolic syndrome, the lipodystrophic mice receive subcutaneous fat transplants,
referred to as distal adipocyte rescue of lipodystrophy (DARL) mice. Littermate controls also receive the fat
transplant, known as DARC mice for distal adipose-receiving control mice. I hypothesize that the metastatic
seeding and dissemination of murine OC cells within the adipocyte-free omentum and associated peritoneum
will be impaired in the absence of local, mature adipocytes. While testing this hypothesis, I will assess how the
loss of omental adipocytes impacts the overall omental architecture in DARL mice. I will analyze the impact of
an adipocyte-free versus adipocyte-rich omentum on tumor growth. Lastly, I will explore the role of
hematogenous and transcoelomic spread to the adipocyte-rich or adipocyte-free omentum and consider
whether omentum cells support tumors as spheroids that disseminate within the peritoneal cavity. I will pursue
these aims under the mentorship of an advisory committee that includes physician-scie...

## Key facts

- **NIH application ID:** 10862572
- **Project number:** 5F30CA281124-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Rachel Mintz
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2023-06-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862572

## Citation

> US National Institutes of Health, RePORTER application 10862572, Mechanisms Underlying the Omental Support of Ovarian Cancer Peritoneal Metastasis (5F30CA281124-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862572. Licensed CC0.

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