# Evaluation of Subtype Specific Collagen Remodeling in Breast Cancer Progression

> **NIH NIH P20** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2021 · $222,000

## Abstract

Project Summary/Abstract
Currently there are no available therapies designed to appropriately target the triple negative/basal breast cancer
subtype (TNBC). Due to the risk of recurrence and metastasis following primary therapy, novel avenues of
intervention must be pursued. The tumor matrix, the material cancer cells are grown on, modulates cellular
proliferation and survival, however a link between a TNBC subtype specific extracellular matrix (ECM) and
mechanisms of TNBC drug resistance has not yet been made. This proposal will identify novel mechanism of
matrix induced drug resistance in TNBC. Using a combination of 3D in vitro screens, murine models of TNBC,
and primary patient samples, Dr. Martin will interrogate novel matrix proteins (collagen IV, XII, and fibronectin)
involved in TNBC drug resistance. The hypothesis of this proposals is: TNBC extracellular matrix enhances drug
resistance through the induction of cellular dormancy. Dr. Martin will use in vitro 3D tumor models to screen the
effects of matrix composition on induction of cellular dormancy and a cancer stem cell phenotype in TNBC.
Furthermore Dr. Martin will determine how cancer cells grown on different matrix composites alter T-cell
activation and proliferation, providing new insight on matrix induced immune evasion. These in vitro screens will
be validated in vivo through the construction and evaluation of conditional knock out of matrix proteins (collagen
IV, XII, fibronectin) in the mammary fat pad of transgenic murine models. Finally the clinical significant of this
study will be verified through the interrogation and histological evaluation of matrix composition, immune
infiltration, and occurrence of cell dormancy in a panel TNBC primary tumors. Dr. Martin will use proteomics to
evaluate the matrix composition of primary TNBC and adjacent matched tissue and correlate these finding with
observed immune infiltration. Additional histological evaluation and confirmation will also be performed. This will
be investigated through the following specific aims: Specific Aim 1. Evaluate the effect of ECM composition on
TNBC drug resistance. Specific Aim 2. Determine the translational relevance of subtype specific ECM
composition.

## Key facts

- **NIH application ID:** 10104817
- **Project number:** 1P20GM135000-01A1
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Elizabeth Martin
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $222,000
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104817

## Citation

> US National Institutes of Health, RePORTER application 10104817, Evaluation of Subtype Specific Collagen Remodeling in Breast Cancer Progression (1P20GM135000-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10104817. Licensed CC0.

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