# Enzymatic Tools for 2D Tissue Localized and Deeper Proteomic Sequencing of Cancer Stromal Proteins

> **NIH NIH R21** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $240,149

## Abstract

Determining the role of stromal proteins in cancer biology has remained difficult due to a lack of tools. Current
tools are qualitative and cannot report on protein sequence variation that is critical to understanding how stromal
proteins help or impede cancer growth and metastasis. Our previous work has shown that bacterial collagenases
can be used to produce stromal proteomes detected by mass spectrometry as 2D distributions on cancer tissues.
We still lack tools that can focus down on target proteins for detailed studies of sequence variation and post-
translational modification. We propose using matrix metalloproteinases (MMPs) as enzymatic tools for targeted
detection of stromal protein sequences in the cancer tissue microenvironment. Aim 1, we will develop and
optimize a suite of MMPs for analysis of stromal sequences in tumor tissue sections. We will produce and
optimize recombinant MMPs specifically for use on 2D solid substrates of tissue sections. We will integrate
sequence information with current qualitative tools, expanding capabilities for stromal protein sequence detection
down to a single cell niche. In Aim 2, we will focus on developing standards for quantitative detection of target
stromal proteins from the tissue microenvironment. We will test the developed technology against a small but
relevant cohort of emergent hepatocellular carcinoma from cirrhosis. Our research team has a unique
combination of expertise for the production, development, and future commercialization of MMPs. The proposal
is transformative since it will allow detection of stromal protein sequence variation from fixed clinical specimens
which is impossible with conventional methods. A long-term objective is to significantly improve the community's
ability to target stromal proteins within the tumor tissue microenvironment for use in basic research, directing
therapies, or prognostic or diagnostic biomarkers.

## Key facts

- **NIH application ID:** 9983646
- **Project number:** 5R21CA240148-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Peggi M Angel
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $240,149
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983646

## Citation

> US National Institutes of Health, RePORTER application 9983646, Enzymatic Tools for 2D Tissue Localized and Deeper Proteomic Sequencing of Cancer Stromal Proteins (5R21CA240148-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9983646. Licensed CC0.

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