# Targeting glycocalyx-mediated mechanisms of tumor metastasis

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $453,981

## Abstract

The ability of cancer cells to migrate away from the primary tumor and colonize distant organs is the ultimate
cause of mortality in cancer. Although many of the molecular and adhesion pathways have been identified,
there is still no effective strategy for limiting metastasis in patients. This is in large part due to our lack of
understanding of the signals that initiate cell invasion into the surrounding tissue and blood vessels. In previous
work, we showed that mechanical forces from flowing interstitial fluid cause profound phenotypic changes in
cancer cells. These forces are transmitted by the cell glycocalyx and influence cell migration, MMP activity and
adhesion molecule expression. We propose that the glycocalyx– by virtue of its role in mechanotransduction—
represents a new and promising target for inhibiting cancer migration and metastasis. In this project, we will
use a tightly-integrated combination of in vitro analyses and in vivo models to determine the components and
pathways responsible for mechanically-induced cell invasion, and then target these mechanisms in a mouse
model of renal carcinoma. Aim 1a will use gene silencing to remove specific components of the glycocalyx to
identify key structures involved in flow-induced activation of metastasis, and Aim 1b will examine the
intracellular signaling pathways downstream of the glycocalyx that might be targeted to inhibit invasion. In Aim
2, we will use a mouse model of renal carcinoma to determine how the glycocalyx components contribute to
local intravasation into the vasculature (Aim 2a) and distant metastasis (Aim 2b). With the key glycocalyx
components and targets identified, we will then use pharmacological interventions to block metastasis (Aim
2c). Finally, we will alter interstitial flow in an orthotopic mouse renal carcinoma to demonstrate the induction of
metastasis by flow in the in vivo setting (Aim 3). These studies have the potential to uncover the fundamental
mechanisms that initiate tumor metastasis, and will open the door to new therapeutic strategies that exploit
mechanobiological signaling pathways.

## Key facts

- **NIH application ID:** 9829099
- **Project number:** 5R01CA204949-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Lance L. Munn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $453,981
- **Award type:** 5
- **Project period:** 2016-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829099

## Citation

> US National Institutes of Health, RePORTER application 9829099, Targeting glycocalyx-mediated mechanisms of tumor metastasis (5R01CA204949-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9829099. Licensed CC0.

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