# Necrosis-mediated circulating tumor cell dissemination

> **NIH NIH F31** · FRED HUTCHINSON CANCER CENTER · 2022 · $39,335

## Abstract

ABSTRACT
Circulating tumor cells (CTCs) give rise to metastases, the major cause of cancer patient mortality. Despite its
long-standing importance, what mediates CTC dissemination remains incompletely understood. One barrier
has been the rarity of CTCs in patients and even more so in mouse models. Recently, I have developed an in
vivo metastasis model for CTCs using rats. Compared with mice, I can robustly collect 10 to 20 times more
blood using rats and obtain many more CTCs. Importantly, I observed that high CTC burden is associated with
intratumoral necrosis, a form of inflammatory cell death. Furthermore, I have found temporal correlation
between increase in intratumoral necrosis and CTC dissemination where there is a sudden 380-fold increase in
CTC counts coinciding with increase in necrosis in the primary tumor. I hypothesize that necrosis in the primary
tumor induces a high CTC dissemination state. I will test this hypothesis by 1) determining whether necrosis in
the primary tumor is sufficient and necessary for a high CTC dissemination state 2) investigating whether CTC
dissemination preferentially occurs in the necrotic regions of the primary tumor and 3) identifying necrotic
tumor microenvironment markers associated with high CTC dissemination states. Uncovering the relationship
between necrosis and CTC dissemination could enable selecting patients with necrotic tumors or surrogate
serum markers of necrosis for more aggressive therapy to disrupt the metastatic process, thereby decreasing
cancer patient mortality.

## Key facts

- **NIH application ID:** 10604553
- **Project number:** 6F31CA260932-02
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Ami Yamamoto
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,335
- **Award type:** 6
- **Project period:** 2022-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10604553

## Citation

> US National Institutes of Health, RePORTER application 10604553, Necrosis-mediated circulating tumor cell dissemination (6F31CA260932-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10604553. Licensed CC0.

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