# Receptor Cross-Talk in Early Metastatic Dissemination

> **NIH NIH R01** · UNIVERSITY OF NOTRE DAME · 2022 · $219,491

## Abstract

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 independent risk factor for OvCa incidence; however disease progression in
the aged host has not been examined experimentally. Experiments in the parent grant address the hypothesis
that host aging induces changes in peritoneal structure and function that influence tumor cell adhesion, matrix
anchoring, and ultimate metastatic success. Ongoing studies in Aim 1 examine age-induced changes in
peritoneal mesothelial cells (MCs) and the resulting impact on MC receptivity to metastatic implantation; Aim2
focuses on aging of the sub-MC collagen matrix, evaluation of aging-induced changes in matrix crosslinking
and biophysical properties, and the influence on metastatic anchoring; and Aim3 investigates Wnt5a as a
mediator of tumor:host cross-talk in the aging peritoneal cavity. In this ‘revision’ grant, we propose to add a
new aim to the parent grant to employ novel technology developed through support from the NCI Innovative
Molecular Analysis Technologies (IMAT) program. This research, conducted by Dr. H-C Chang, developed a
novel solid-state nanopore technology for isolation and lysis of exosomes from complex biofluids and capture
and quantitation of exosomal microRNAs. Using this technology, the new Aim 4 of the revision application will
assess the role of bi-directional tumor:host communication via exosome-mediated miRNA delivery in metastatic
progression in the context of host aging. Successful completion of the proposed experiments will provide
rigorous functional validation and benchmarking of the solid-state nanopore technology in an interesting and
relevant model system. Simultaneously we will enhance the impact of the parent grant and provide
unprecedented insight into molecules and events that mediate tumor:host communication in the aged host.

## Key facts

- **NIH application ID:** 10355901
- **Project number:** 3R01CA109545-14S1
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Mary Sharon Stack
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $219,491
- **Award type:** 3
- **Project period:** 2006-07-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355901

## Citation

> US National Institutes of Health, RePORTER application 10355901, Receptor Cross-Talk in Early Metastatic Dissemination (3R01CA109545-14S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10355901. Licensed CC0.

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