# Organ-on-chip bioreactors for recreating breast to brain metastases

> **NIH NIH R21** · VANDERBILT UNIVERSITY · 2022 · $181,543

## Abstract

30 line summary:
The objective of this proposal is to develop for the scientific community validated assays based
on organ on chip systems that will enable interrogating the neuron dependent regulators of breast-
to-brain metastasis and related complications such as vasogenic edema associated with blood
brain barrier disruption. Brain metastases (with breast cancer being second largest cause) and
their associated neurologic disabilities are particularly serious as they result in very short life
expectancies and reduced quality of life. There is a significant lack of effective therapeutic
regiments due to presence of blood brain barrier which precludes the delivery of multiple
chemotherapeutic drugs into the central nervous system (CNS). We will use the NeuroVascular
Unit (NVU) tissue chip, an organ-on-chip equivalent of the blood-brain-barrier comprised of
neurons, astrocytes, brain pericytes and brain microvascular endothelial cells. We will evaluate
its suitability to study the neuronal regulation of breast-to-brain metastasis with particular
emphasis on measuring the specific role of neurons on metastatic disease expansion,
colonization and the associated changes to the metastatic microenvironment. Furthermore, we
will evaluate the NVU coupled to a Mammary Gland Thick Tissue bioreactor (MG-TTB) as a
complete primary-to-secondary site oncology-on-chip system for advanced study of breast-to-
brain metastasis. MG-TTB is a microfluidic bioreactor developed by our group for drug
assessment of tumorigenic mammary epithelial cells that is currently in use for toxicant
assessment, monitoring toxicant-dependent changes to cellular functions, and drug assessment
of tumorigenic mammary epithelial cells cultured under defined physical and chemical tumor
microenvironments. The MG-TTB is on the same physical scale and shares similar materials and
hardware with NVU that will allow seamless integration of these units to probe primary-to-
secondary tumor dissemination. Our aims to validate the suitability of NVU for study of breast-to-
brain metastasis processes are as follows: 1) Determine the neuron dependent dynamic changes
to metastatic tumor microenvironment driven by breast cancer brain metastases seeded within
the NVU. 2) Determine the neuron dependent role into breast-to-brain metastasis by evaluating
their contribution in tumor extravasation of the NVU blood brain barrier.

## Key facts

- **NIH application ID:** 10416014
- **Project number:** 5R21CA249770-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** LISA Joy MCCAWLEY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $181,543
- **Award type:** 5
- **Project period:** 2021-06-02 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10416014

## Citation

> US National Institutes of Health, RePORTER application 10416014, Organ-on-chip bioreactors for recreating breast to brain metastases (5R21CA249770-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10416014. Licensed CC0.

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