# Biomaterial Mimicry of Dynamic Matrix Stiffening During Tumor Progression

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $343,103

## Abstract

Project Summary
Tissue stiffens in and around a tumor, making it clear that physical properties of a tissue change as tumors
develop. While the genetic and biochemical events initiating cell transformation have been studied for decades,
this proposal is aimed at expanding our knowledge of how, why, and to what extent physical environmental
parameters, e.g. stiffness, drive tumor formation. Since these niche are dynamic, we have developed a model
hydrogel system that stiffens “on-demand” to understand the physical dynamics of cancer, i.e. methacrylated
hyaluronic acid (MeHA) hydrogels. This material enables reductionist controlled unparalleled in most in vitro
approaches and permits real time monitoring of mammary epithelial cells to observe their individual and
collective responses to a changing environment in real time. MeHA hydrogels will be stiffened after the
formation of mature acinar structures to determine how, why, and to what extent this induces the early stages
of epithelial-to-mesenchymal transition (EMT). We will then determine whether this process is cell autonomous
and how it couples with known inductive mechanisms, e.g. TGF-beta signaling. However significant
heterogeneity exists in tumor initiation in vivo, and since our model offers a simple system in which to examine
stiffness-induced EMT, in a second aim we will study whether EMT is caused by individual or collective
decisions within the acinus. We will perform a detailed analysis of force transmission and mechanotransduction
within acini, the MeHA hydrogel, and the surrounding basement membrane to dissect the molecular machinery
used by individual or collections of cells to communicate and coordinate EMT. Finally we will test the roles of
the identified EMT regulators in promoting tumor invasion and metastasis in vivo. This unique materials-based
approach to EMT and malignant transformation, this proposal will significantly improve our understanding of
EMT, its plasticity, and its regulators in vitro and apply it to an in vivo model.

## Key facts

- **NIH application ID:** 9962886
- **Project number:** 5R01CA206880-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Adam J Engler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,103
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962886

## Citation

> US National Institutes of Health, RePORTER application 9962886, Biomaterial Mimicry of Dynamic Matrix Stiffening During Tumor Progression (5R01CA206880-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9962886. Licensed CC0.

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