# Characterizing the effects of extracellular matrix viscoelasticity on dendritic cell activation

> **NIH NIH K00** · HARVARD UNIVERSITY · 2022 · $85,795

## Abstract

PROJECT SUMMARY
 Cancer cells, extracellular matrix (ECM) and carcinoma-associated fibroblasts (CAFs) are three critical
factors contributing to tumor progression in colorectal cancer and squamous cell carcinoma, among other
cancer types. CAFs are often associated with the development of high-grade malignancies of poor prognoses
because CAFs secrete metastasis-promoting cytokines and abnormally deposit collagen, facilitating integrin-
dependent cancer invasion and forming hindrance of anti-cancer drug delivery. Despite the detailed studies
about the role of CAFs in tumor progression, the mechanism by which stromal cells become CAFs is still not
clear: how normal fibroblasts in stroma are transformed to CAFs during early stages of cancer? In this project, I
will test the hypothesis that cancer cells facilitate CAF induction by mechanically reorganizing extracellular
matrix and thus breaking down the diffusion barrier of CAF-inducing factors. A coculture system containing
colorectal cancer spheroids and multiple types of stromal cells as the testing platform will be constructed for
the preliminary tests. If proven valid, I will use my hypothesis to develop new treatments where ECM
remodeling is suppressed to decrease the rate of tumor progression in colorectal cancer. Two treatment
strategies will be tested: (1) direct applying ECM crosslinking agents in the tumor microenvironment; (2)
implanting genetically engineered fibroblasts secreting ECM crosslinking enzymes and other anti-cancer
biomolecules. Colorectal cancer mouse models will be used to evaluate the efficacy of the new treatments.

## Key facts

- **NIH application ID:** 10554654
- **Project number:** 4K00CA253759-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Wei-Hung Jung
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $85,795
- **Award type:** 4N
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10554654

## Citation

> US National Institutes of Health, RePORTER application 10554654, Characterizing the effects of extracellular matrix viscoelasticity on dendritic cell activation (4K00CA253759-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10554654. Licensed CC0.

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