# Mechanical determinants of organ-selective metastatic colonization, dormancy and outgrowth

> **NIH NIH U54** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $1,723,529

## Abstract

Overall: PROJECT SUMMARY
Metastatic disease is responsible for the vast majority of cancer mortality. Understanding of the fundamental
mechanisms leading to metastatic cancer has been hampered by the need for models that replicate the step-
wise metastatic process in vivo, yet are amenable to tight control and facilitate high-resolution, time-lapse
imaging and quantitative analysis of cell behavior. Over the past decade, our team has developed in vivo and
in vitro methods capable of simulating many steps of the metastatic cascade including tumor cell invasion,
intravasation, trapping in the microcirculation or adhesion to the vessel walls, and extravasation into the
surrounding extracellular matrix. In parallel, we have developed computational studies that provided detailed
insights often not possible through experiments. This collective prior work has shed new light on central aspects
of single-cell and collective cell behavior during metastasis, and identified mechanical adaptations and
vulnerabilities of the tumor cell with promise for targeted interventions. The goal of our proposed U54 Center is
to employ these developed assays and methods in combination with new measurement techniques to interrogate
the full spectrum of stressors experienced by tumor cells in the metastatic niche during arrest and extravasation,
and couple these with parallel studies of changes in chromatin structure and the transcriptome of tumor cells
(Core B). These changes are critical to mechano-adaptation of the tumor cells towards an organ-preferential
initiation of a metastatic colony or transition to dormancy. A hallmark of our proposed center is the use of state-
of-the-art in vitro (Project 1) and in vivo (Project 2) experiments and computation (Core A) to uncover and probe
the factors that ultimately determine tumor cell fate. We anticipate that such integrated studies will provide new
insights into metastatic cancer, not possible by the use of any method alone, and enhance our ability to identify
and screen for new therapies to inhibit the tendency for metastatic spread of disease.

## Key facts

- **NIH application ID:** 10490281
- **Project number:** 5U54CA261694-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** ROGER D KAMM
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,723,529
- **Award type:** 5
- **Project period:** 2021-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490281

## Citation

> US National Institutes of Health, RePORTER application 10490281, Mechanical determinants of organ-selective metastatic colonization, dormancy and outgrowth (5U54CA261694-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10490281. Licensed CC0.

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