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

Award Number: R01CA270030
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/20/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $372,340 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Biology Research	000	3	1/13/2025	NON-COMPETING CONTINUATION	$372,340
														Subtotal = $372,340

Issue Date FY: 2024 ( Subtotal = $393,846 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Cancer Biology Research	000	2	2/5/2024	NON-COMPETING CONTINUATION	$373,117
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Cancer Biology Research	001	2	4/24/2024	NON-COMPETING CONTINUATION	$20,729
														Subtotal = $393,846

Issue Date FY: 2023 ( Subtotal = $409,948 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Cancer Biology Research	000	1	2/20/2023	NEW	$409,948
														Subtotal = $409,948

Grand Total All Awards = $1,176,134

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

Award Number: R01CA270030

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/20/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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