# Promotion of metastasis by apoptotic cells

> **NIH NIH U01** · UNIVERSITY OF WASHINGTON · 2024 · $721,836

## Abstract

Project Summary/Abstract
 The goal of most cancer treatments is to induce the apoptotic death of tumor cells; in many cases these
treatments also induce substantial off-target apoptosis in healthy tissues. Even in the absence of therapy, the
majority of prospective metastatic cells die by apoptosis, resulting in the early metastatic niche being rich in
apoptotic cell material. While numerous studies have focused on the features of tumor cells that allow them to
survive and metastasize in the face of such treatments, less attention has been paid to the influence of dying
cells themselves on cancer progression. The work proposed here will investigate the hypothesis that apoptotic
cells drive efficient metastatic spread of healthy cancer cells, because they initiate a cascade of platelet
recruitment, coagulation, and myeloid cell reprogramming at metastatic sites. We will address this hypothesis
by focusing on three Aims: First, we will address the role of phosphatidylserine exposure on apoptotic cells in
recruiting platelets and promoting tumor cell survival within the intravascular niche upon arrival of
metastasizing cells to the lung. Second, we will examine the interface between apoptotic cells, cancer cells,
and the myeloid immune network of the lung, during extravasation and establishment of the metastatic niche.
Third, we will study the effects of apoptotic cells on spontaneous metastasis from a primary tumor, and test
whether blocking pro-metastatic features of apoptotic cells can reduce metastasis in this setting. While our
work is focused on the fundamental processes by which apoptotic cells influence metastasis, we suggest that it
may point toward therapeutic combinations that prevent metastasis.

## Key facts

- **NIH application ID:** 10869708
- **Project number:** 1U01CA289564-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Mark Bryan Headley
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $721,836
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869708

## Citation

> US National Institutes of Health, RePORTER application 10869708, Promotion of metastasis by apoptotic cells (1U01CA289564-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10869708. Licensed CC0.

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