# The Role of Hematopoietic Stem and Progenitor Cells in Solid Tumor Growth and Response to Radiation Therapy

> **NIH NIH R15** · OAKLAND UNIVERSITY · 2022 · $449,795

## Abstract

PROJECT SUMMARY
A major component of many solid tumors, including lung cancers, are bone marrow (BM)-derived immune cells
that migrate to tumors and aid in their continued growth. While the activity of these cells including tumor
associated macrophages (TAMs) has been the subject of intense investigation, we recently identified that BM-
derived hematopoietic stem and progenitor cells (HSPCs) are also present in growing tumors and can be
functionally maintained intratumorally for long periods of time. Interestingly, the numbers of HSPCs present in
tumors directly correlates to the eventual regrowth rates of tumors following radiation therapy (RT). The data
suggests that HSPCs represent another important cell population involved in tumor biology, however; their
mechanism of action is still unclear. Filling this gap in knowledge will add to the ever-changing understanding of
tumor biology. The objective of this proposal is to determine how HSPCs are maintained in tumors and how
HSPCs promote tumor regrowth post-RT. Our preliminary data support the idea that HSPCs are maintained
through interactions of the integrin CD49f and laminins present within the tumor extracellular matrix. In Specific
Aim 1, we will show that this interaction is indeed responsible for HSPC maintenance using in vitro and in vivo
strategies that block or enhance this interaction followed by analysis of their effects on HSPC functionality. We
will also define the intracellular signaling pathways involved in this process with initial studies focusing on focal
adhesion kinase (FAK) signaling. These studies will characterize for the first time a tumor specific niche capable
of maintaining HSPCs outside of the BM. In Specific Aim 2, we will demonstrate that tumor treatment with RT
exacerbates HSPC migration to tumors and concomitantly disrupts the interaction between CD49f and laminin.
We will also show that RT produces tumor microenvironments that favor the differentiation of these ‘released’
HSPCs into tumor supportive macrophages (specifically M2 polarized) to aid in tumor recovery. We will also test
the effects of blocking the activity of HSPCs on tumor growth and regrowth post-RT. By completing the proposed
studies, our long-term goal is to use the knowledge gained to make a significant contribution towards the
development of more robust treatment strategies for patients suffering with solid tumor based cancers.

## Key facts

- **NIH application ID:** 10359313
- **Project number:** 1R15CA254006-01A1
- **Recipient organization:** OAKLAND UNIVERSITY
- **Principal Investigator:** Gerard James Madlambayan
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $449,795
- **Award type:** 1
- **Project period:** 2022-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359313

## Citation

> US National Institutes of Health, RePORTER application 10359313, The Role of Hematopoietic Stem and Progenitor Cells in Solid Tumor Growth and Response to Radiation Therapy (1R15CA254006-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10359313. Licensed CC0.

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