# Investigating the role of the extracellular matrix in metastasis and chemo-resistance

> **NIH NIH R00** · TUFTS UNIVERSITY MEDFORD · 2020 · $249,000

## Abstract

Project Summary
Metastasis, the dissemination of cells from the primary tumor, is the leading cause of death in cancer patients.
For metastatic breast cancer, chemotherapy remains the standard of care. While the benefits of chemotherapy
for the treatment of metastatic disease have been well documented, over 50% of triple-negative breast cancer
patients become resistant to chemotherapy. Increasing our understanding of the mechanisms driving
metastasis and drug resistance will help identify biomarkers that can be used to predict them, and characterize
targetable signaling pathways to that can be used to prevent them. It is now well appreciated that the tumor
microenvironment can contribute to tumor progression and metastasis. The extracellular matrix (ECM), forms a
complex scaffold of proteins that provides both structure and signals to the tumor cells. However, its role in
driving invasion and metastasis and how it could affect response to chemotherapy remains unexplored.
The main goal of this proposal is to investigate the role of the ECM in metastasis and chemo-resistance, using
an interdisciplinary approach that will combine cell biology, intravital imaging, systems biology and implantable
devices. First, we have shown that gradients of fibronectin can promote directional motility of tumor cells, a
process important for metastasis. When highly metastatic tumor cells are subject to gradients of EGF and
fibronectin simultaneously, they will invade even more than with each cue alone. The goal of Aim 1 is to
investigate the contribution of ECM versus growth factor cues during local invasion and metastatic
colonization. Second, preliminary investigation into the effect of chemotherapeutic drugs on highly invasive
tumor cells revealed that they can have differential effects on cell proliferation and migration, and can also
regulate ECM sensitivity and organization. In Aim 2, I will identify ECM combinations that affect cell growth and
migration in response to clinically relevant chemotherapy regimens and perform a CRISPR knockout screen of
ECM-regulator proteins to identify novel genes regulating chemo-sensitivity.
I also propose an extensive training program that will support my transition to independence. The research
environment provided by the Koch Institute at MIT is outstanding, and offers unequaled opportunities for
scientific discussion, collaboration between biologists and engineers, and career development. I have
assembled an exceptional team to help me achieve my goals: Prof. Frank Gertler, expert in cell motility, and
Prof. Michael Hemann, expert in studying mechanisms of drug resistance will be my mentors. Prof. Richard
Hynes, a pioneer in ECM research, and Prof. Doug Lauffenburger, leader in cancer systems biology, will be
collaborators and members of my mentoring committee. My training will also involve mentoring students,
attending and presenting my work at meetings to become an active member of the ECM and cancer
communities, and sci...

## Key facts

- **NIH application ID:** 9864053
- **Project number:** 5R00CA207866-05
- **Recipient organization:** TUFTS UNIVERSITY MEDFORD
- **Principal Investigator:** Madeleine Julie Oudin
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-03-08 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864053

## Citation

> US National Institutes of Health, RePORTER application 9864053, Investigating the role of the extracellular matrix in metastasis and chemo-resistance (5R00CA207866-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864053. Licensed CC0.

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