# Microfluidic platform for tumor cell invasion

> **NIH NIH R01** · CORNELL UNIVERSITY · 2020 · $368,288

## Abstract

Project Summary
Cancer metastasis accounts for over 90% of all cancer deaths. A limiting step in cancer metastatic cascade is
for tumor cells to migrate towards, interact with and squeeze through the blood vessel wall before
disseminating to secondary tumor sites via the blood circulation. Biophysical forces, including interstitial and
intramural flows, have shown to play critical roles in regulating adhesion molecules, spatial cytokine
distributions and tissue architecture; all of which contribute to tumor cell invasion within 3D biomatrix. Despite
the clinical importance, roles of biophysical forces in tumor cell transendothelial migration (TEM) are poorly
understood. This is in part due to the lack of in vitro tools that are able to follow tumor cell transmigration
events in real time, and with well controlled biological flows. Current animal cell invasion assay, the Boyden
Chamber, is limited because it is difficult to recreate complex tumor microenvironment. In addition, the results
are population based at two time end points. Intravital imaging has advanced significantly our understanding
about the interplays between tumor microenvironment and TEM in a physiologically realistic setting. However,
it is difficult to dissect the contribution of individual environmental cues to TEM processes. The goals of the
proposed research are to develop a physiologically realistic microfluidic model with well controlled tumor
microenvironment for studies of tumor cell TEM processes; and to identify tumor microenvironment that
promotes TEM. To achieve these goals, we will develop an organotypic microfluidic model for real time
imaging of tumor cell TEM events under well controlled micro-environment. We will use the location of
spheroid and cell streaming event to guide TEM imaging sites. Using the microfluidic model, we will
explore the relations between single tumor cell properties and TEM activities under well controlled
interstitial and intramural flows. Previous work from the PI’s lab and others have indicated that interstitial
flows critically regulate tumor cell migration within 3D biomatrix. Here, we hypothesize that tumor cells’
TEM capabilities are closed correlated with cells’ microenvironment including fluid flows. The proposed
project is innovative because it represents the first generation of organotypic microfluidic platform that
includes both interstitial and intramural flows, moving the current microfluidic tumor model towards a
physiologically realistic direction. Lessons learned here will eventually lead to knowledge important for
developing novel diagnostic or/and treatment strategies for cancer. This platform can be readily extended
for use in other biological systems where TEMs are important including immune cell trafficking.

## Key facts

- **NIH application ID:** 9985757
- **Project number:** 5R01CA221346-04
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Mingming Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,288
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985757

## Citation

> US National Institutes of Health, RePORTER application 9985757, Microfluidic platform for tumor cell invasion (5R01CA221346-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9985757. Licensed CC0.

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