# Role of Osterix+ Osteolineage Cells in Primary and Metastatic Breast Cancer

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $393,846

## Abstract

ABSTRACT
In order to survive, grow and metastasize, tumors need the support of a favorable host environment. Local
changes in normal cells in close proximity to a developing tumor can create a favorable tumor micro-environment
(TME) that is necessary for tumor growth. Mesenchymal populations, including cancer-associated fibroblasts
(CAFs), secrete pro- tumorigenic and immune suppressive factors, and produce extracellular matrix to create a
stiffer, tumor-conducive soil. Several CAF subsets with specific functions have been identified, however, whether
distinct CAF subsets derive from the same progenitor that acquire functional specificity during tumor progression
or from different progenitors committed to give rise to a specific CAF population, is under investigation.
We recently made the unexpected observation that cells expressing bone osteolineage marker Osterix (Osx) are
present in the TME of tumors outside the bone and support tumor growth. In adult animals, Osx is expressed by
committed osteoblasts (OB) and drives their differentiation. Surprisingly, we detected Osx in stromal cells,
isolated from various breast cancer tumors, expressing CAF and OB makers, and in the tumor-associated stroma
of patients with breast carcinomas. Co-injection of Osx+ cells with tumor cells enhance tumor growth.
Importantly, Osx expression correlates with poor prognosis in breast cancer. Based on these rather unexpected
findings, we hypothesize that bone-derived osteolineage Osx+ cells represent a novel subset of tumor infiltrating
stromal populations contributing to tumor progression and CAF diversity. Aim 1 will determine the functional
relevance of Osx+ cells in the TME and pre-metastatic sites; Aim 2 will determine the origin of Osx+ cells in the
TME and pre-metastatic sites. This information will broaden the concept of cellular heterogeneity within the TME
and offer a new platform for targeting the stroma with the purpose of inhibiting tumor growth.

## Key facts

- **NIH application ID:** 10792600
- **Project number:** 5R01CA270030-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Roberta Faccio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $393,846
- **Award type:** 5
- **Project period:** 2023-02-20 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792600

## Citation

> US National Institutes of Health, RePORTER application 10792600, Role of Osterix+ Osteolineage Cells in Primary and Metastatic Breast Cancer (5R01CA270030-02). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10792600. Licensed CC0.

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