# Metastasis and biophysics of clusters of circulating tumor cells in the microcirculation

> **NIH NIH U01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $594,889

## Abstract

ABSTRACT
Circulating tumor cells drive metastasis when they travel from primary tumors to distant organs via the
circulation. Multicellular clusters of circulating tumor cells though less frequently observed in blood, are
much more likely to establish metastases than individual circulating tumor cells and the presence of tumor
clusters in blood has been associated with dramatically worse prognoses in patients. Although there are
many suspected explanations for their greater metastatic potentials, much is still unknown about the
behavior of clusters, especially in the narrow vessels of the body. Recent evidence has demonstrated that
cluster transiting through narrow constrictions experience dynamic changes to structure and organization.
Forces in the microcirculation cause clusters to reversibly re-organize into single-file chains to enable
transit through narrow capillary-sized vessels and nuclear envelopes are ruptured and rapidly repaired
during migration events through narrow constrictions. Two biophysical parameters within clusters,
cellular adhesion strengths and nuclear mechanics, are vital for these behaviors. Because of the important
role that these parameters play in many aspects of metastatic progression, we hypothesize that these
parameters modulate the biophysical responses of clusters to physical forces in the microcirculation, and
that these interactions play a significant role in the competitive edge that clusters have edge over
individual cancer cells for seeding metastases. To this end, we propose three specific aims. In aim 1, we
will develop next generation models of the human microcirculation with rounded networks of endothelial
cell coated microfluidic devices and geometry matched computational simulations. In aim 2, we will
explore how intercellular adhesions affect the biophysical responses and metastasis-forming abilities of
homogeneous versus heterogeneous clusters in the microcirculation through the use of our developed
models. Finally, in aim 3 we will study the physical basis for nuclear envelope rupture, DNA-damage,
genetic instability and other DNA-level affects that are involved in metastatic progression. Understanding
the interplay between the biophysics and biology of clusters within the microcirculation will elucidate
mechanisms that can be used to combat the progression of cluster-initiated metastases.

## Key facts

- **NIH application ID:** 10429911
- **Project number:** 5U01CA214297-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Daniel A. Haber
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $594,889
- **Award type:** 5
- **Project period:** 2018-05-08 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429911

## Citation

> US National Institutes of Health, RePORTER application 10429911, Metastasis and biophysics of clusters of circulating tumor cells in the microcirculation (5U01CA214297-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10429911. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*