# The Role of Platelets in Establishing the Lung Pre-Metastatic Niche in Breast Cancer

> **NIH NIH K99** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $178,200

## Abstract

PROJECT SUMMARY
Tumor metastasis remains responsible for >65% of cancer-associated mortality and nearly all
breast cancer deaths. Given the difficulties in treating metastatic disease, preventive approaches
that block the successful dissemination of tumor cells to distant organs like the lung offer an
attractive and under-researched therapeutic strategy for breast cancer patients at risk of
metastatic disease. Primary tumors increase metastatic efficiency by reprogramming the
microenvironment of distant organs before the arrival of circulating tumor cells. These tumor-
permissive sites are commonly referred to as the “pre-metastatic niche” (PMN) and undergo a
series of cellular and structural adaptations that support arriving tumor cells, including the
recruitment of inflammation-promoting and immunosuppressive cells, neoangiogenesis, and
stromal remodeling. Despite their archetypal roles in hemostasis, blood platelets are integral to
inflammatory lung diseases and regulate many of the hallmarks adopted by the PMN. I, therefore,
hypothesize that platelets promote the lung PMN. My preliminary data support this statement,
demonstrating that platelets are sequestered in pre-metastatic lungs and that lowering platelet
counts reduces immune cell recruitment to the lung PMN. To expand on these initial findings, this
research will determine the contributions of platelets to the lung PMN (Aim 1), elucidate
mechanisms by which platelets impact the lung pre-metastatic environment (Aim 2), and test if
therapeutically targeting pre-metastatic platelet number or function impairs metastasis (Aim 3).
The technical skills and scientific expertise I will obtain throughout the K99 award period will prove
instrumental in my transition into an independent researcher, with the long-term goal to develop
novel preventative and adjuvant therapeutic strategies for patients at risk of metastatic breast
cancer. To reach these long-term goals, I have outlined a detailed career development plan, which
will provide me with the technical and leadership skills to establish a successful research
laboratory. The K99 phase of research will be conducted under the excellent (co)mentorship of
Drs. Elisabeth Battinelli and Sandra McAllister at the Hematology Division of Brigham and
Women’s Hospital. My Research Advisory Committee and collaborators are leading experts in
the breast cancer PMN (Dr. Moses), platelet production (Dr. Italiano), and targeting platelets for
breast cancer therapy (Dr. Chen). This K99/R00 award will provide me unparalleled support for
my successful transition to an independent investigator studying platelet and cancer biology.

## Key facts

- **NIH application ID:** 10894750
- **Project number:** 5K99CA283008-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Harvey George Roweth
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $178,200
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894750

## Citation

> US National Institutes of Health, RePORTER application 10894750, The Role of Platelets in Establishing the Lung Pre-Metastatic Niche in Breast Cancer (5K99CA283008-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10894750. Licensed CC0.

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