# Decoupling the Mechanobiology of Neutrophil Extracellular Traps (NETs) in Tumor Metastasis

> **NIH NIH SC2** · NORTH CAROLINA AGRI & TECH ST UNIV · 2020 · $124,748

## Abstract

Arvind Chandrasekaran
Abstract
Mechanical rigidity of a tumor microenvironment (TME) and the surrounding stroma is an important
physical parameter that affects cellular functions. Increased Extracellular Matrix (ECM) stiffness is
beginning to be considered as a driving factor in tumor initiation, contributing significantly in
mediating the transition from dormant to malignant states. However, understanding of the initial
mechanisms leading to the pre-pathological amplification in matrix rigidity is still evolving.
Neutrophils form the most abundant cell population of the innate immune system, representing 50–
60% of circulating white blood cells and are the first line of defense during inflammation and
infection. Under certain conditions, activated neutrophils undergo a form of programmed cell death
by releasing decondensed chromatin, histones and DNA into their surrounding ECM, forming three-
dimensional protein web structures called Neutrophil Extracellular Traps (NETs). Recent evidences
suggest that NETs that are formed around a tumor could be directly associated with tumor
metastasis progression. However, the exact mechanisms and the signaling pathways of NETs
interactions with the tumor cells and the stroma are still under research.
The primary objective of this project proposal is to decipher the mechanobiological implications of
NETs, i.e regulation of the mechanical properties of the tissues (such as stiffness and porosity) due
to the formation of NETs, specifically in the context of tumor metastasis. The fundamental hypothesis
of this proposal is that NETs accumulating around a tumor bind to the proteins present in the ECM,
and stiffen the matrix sufficiently enough to induce downstream biological effects related to tumor
growth and invasion. The long-term goal of this project is to understand the mechanobiological
organization and regulation of NETs in disease processes. A better comprehension of this concept
could have paradigm-shifting implications with respect to the development of suitable therapeutic
interventions, not just within the context of tumor metastasis but also towards the pathogenesis of
other infectious and autoimmune diseases.

## Key facts

- **NIH application ID:** 9934822
- **Project number:** 1SC2GM136523-01
- **Recipient organization:** NORTH CAROLINA AGRI & TECH ST UNIV
- **Principal Investigator:** Arvind Chandrasekaran
- **Activity code:** SC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $124,748
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934822

## Citation

> US National Institutes of Health, RePORTER application 9934822, Decoupling the Mechanobiology of Neutrophil Extracellular Traps (NETs) in Tumor Metastasis (1SC2GM136523-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934822. Licensed CC0.

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