# Detection and characterization of cell type-specific extracellular vesicles in obesity-driven hepatocellular carcinoma

> **NIH NIH R21** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $204,870

## Abstract

PROJECT SUMMARY
The worldwide prevalence of obesity has reached pandemic proportions. An association between fat
accumulation or hepatosteatosis and hepatocellular carcinoma (HCC) development has been long known.
Obesity-induced hepatosteatosis, together with its more severe complication nonalcoholic steatohepatitis
(NASH), classified as the nonalcoholic fatty liver disease (NAFLD) affects up to 40% of the US population.
Based on correlative and bench studies, several mechanisms have been proposed to explain how obesity
increase cancer risk. An important finding that accounts for the tumor-promoting effect of obesity is the low-
grade, aberrant inflammatory response, which results in the elevated production of cytokines, such as TNF
and IL-6. Studies with mouse models demonstrated that obesity-promoted HCC development is dependent
on the enhanced production of these inflammatory cytokines. However, critical questions concerning how the
aberrant inflammation in obesity is initiated have been yet to be clearly defined.
We hypothesize that in obesity, extracellular vesicles (EVs) derived from hepatocytes become pathogenic
and drive recipient immune cells, such as neutrophils and monocytes/macrophages, towards abnormal
inflammation associated with the development of HCC. To demonstrate this hypothesis, we will establish two
novel systems; A) a new mouse line in which specific cell/tissue-derived EVs are selectively labeled with
green fluorescent protein (GFP), and B) a simple, yet powerful electrokinetic-based micro-device that can
rapidly extract EVs based on their dielectric properties from biofluids with high purity and yield. With these
systems, we aim to
 1) determine if H-EVs become pathogenic and induce aberrant inflammation leading to HCC, and
 2) isolate H-EVs through the novel dielectrophoretic (DEP) technology and assess their pro-
 inflammatory trait.
This study will lead us to demonstrate the pathogenicity of hepatocyte-derived EVs, which potentially provides
a novel mechanism for the development of HCC and the EV biomarker for the disease.

## Key facts

- **NIH application ID:** 9936127
- **Project number:** 5R21CA240664-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Takahisa Nakamura
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $204,870
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936127

## Citation

> US National Institutes of Health, RePORTER application 9936127, Detection and characterization of cell type-specific extracellular vesicles in obesity-driven hepatocellular carcinoma (5R21CA240664-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9936127. Licensed CC0.

---

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