# Chemo-Mechanical Feedback between CAFs, Leader Cells, and the Extracellular Microenvironment Regulates Leader Cell Regulated Collective Cell Migration

> **NIH NIH F32** · WASHINGTON UNIVERSITY · 2022 · $69,802

## Abstract

Project Summary/Abstract
The impact of cancer associated fibroblasts (CAFs) and the extracellular microenvironment (ECM) in cancer
metastasis has become more and more appreciated. The tumor microenvironment consists of multiple
compartments: cellular, physical, and chemical. Each compartment in cancerous tissues differs greatly from
normal tissue, yet the role that each plays in metastasis and how they affect each other is poorly understood.
CAFs have been shown to promote tumor cell metastasis in part by altering the local collagen
microenvironment. CAFs can enhance cancer metastasis in 3 ways; (1) direct association between CAFs and
leader cells within the tumor, (2) CAF mechanical alterations of the local microenvironment, and (3) CAF
secretions that can signal for tumor metastasis and collagen remodeling. How the chemo-mechanical feedback
between CAFs, cancer cells, and the ECM remains poorly understood. Here, our goal is to elucidate the
chemo-mechanical feedback function of CAFs on leader cells and the microenvironment that facilitates
directed collective cell migration. (1) Quantify the impact of CAFs on collective cell migration and ECM
remodeling. (2) To examine the effect of the CAF secretome on local collagen structure and function. We will
utilize microfluidic cell-based invasion assays in conjunction with primary breast tumor organoids or
reconstituted breast tumor organoids (non-migratory mammary cells mixed with isolated leader cells or CAFs)
to probe the effect of CAFs on collective cell migration. We will isolate the role of mechanical forces generated
by CAFs within the tumor on leader cell function and the effect of CAF generated forces on collagen
deformation and remodeling (1). We will then compare the mechanical effect of CAFs on collective migration to
that of the chemical CAF secretions on collagen remodeling (2). We aim to quantify the relative role of both
mechanical and chemical models to generate a predictive model of CAF function on collective cell migration.
We will verify this model by using engineering techniques to manipulate the microenvironment and observe the
effect on collective migration. We will combine this with biological techniques to genetically manipulate CAFs
and leader cells to identify how CAFs are capable of effecting collective cell migration.

## Key facts

- **NIH application ID:** 10537168
- **Project number:** 1F32CA275212-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Vasilios Aris Morikis
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,802
- **Award type:** 1
- **Project period:** 2022-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537168

## Citation

> US National Institutes of Health, RePORTER application 10537168, Chemo-Mechanical Feedback between CAFs, Leader Cells, and the Extracellular Microenvironment Regulates Leader Cell Regulated Collective Cell Migration (1F32CA275212-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10537168. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*