# Receptor Cross-Talk in Early Metastatic Dissemination

> **NIH NIH R01** · UNIVERSITY OF NOTRE DAME · 2021 · $330,244

## Abstract

Ovarian cancer (OvCa) is the most fatal gynecologic cancer with a low (<27%) 5-year survival rate. Survival
of women with OvCa has not changed appreciably in over 30 years and most women diagnosed will die of
painful complications that arise as a result of widely disseminated intraperitoneal (IP) metastasis.
Epidemiologic data indicate that age is a significant risk factor for OvCa incidence; however disease
progression in the aged host has not been examined experimentally. In the previous funding period we
developed a suite of new in vitro, ex vivo, and in vivo model systems and imaging modalities with which to
examine the mechanistic link between host age and ovarian cancer metastatic success. Using these models,
our preliminary data show age-related alterations in peritoneal mesothelial cells (MC) and sub-mesothelial
collagen together with enhanced tumor burden in aged relative to young mice and suggest that Wnt5a can
function as a mediator of tumor:host cross-talk in the peritoneal cavity. Experiments in the current project will
address the hypothesis that host ageing induces changes in peritoneal structure and function that influence
tumor cell adhesion, matrix anchoring, and subsequent metastatic success. To address this hypothesis, Aim
1 will examine age-induced changes in peritoneal MCs, the response of aged MCs to compression and
strain, and the resulting impact on MC receptivity to metastatic implantation. Aim2 will focus on ageing of the
sub-MC collagen matrix, evaluate age-induced matrix crosslinking and biophysical properties, and the
ultimate effect on metastatic anchoring. Aim3 will investigate Wnt5a as a mediator of tumor:host cross-talk in
the ageing peritoneal cavity. Successful completion of these aims will provide unparalleled insight into ageing
and IP metastasis. As the high mortality of OvCa is directly attributable to IP metastasis, innovative
approaches that integrate data from both tumor and host will identify critical determinants of metastatic
success for future targeted intervention.

## Key facts

- **NIH application ID:** 10090457
- **Project number:** 5R01CA109545-13
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Mary Sharon Stack
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $330,244
- **Award type:** 5
- **Project period:** 2006-07-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10090457

## Citation

> US National Institutes of Health, RePORTER application 10090457, Receptor Cross-Talk in Early Metastatic Dissemination (5R01CA109545-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10090457. Licensed CC0.

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