# Project 2: Metabolism-Mediated Changes of Microvesicle Biogenesis

> **NIH NIH U54** · CORNELL UNIVERSITY · 2020 · $390,556

## Abstract

Project Summary – Project 2 
The programmatic goals of this PSOC application are to understand how the physical characteristics of 
tumor cells within their 3D microenvironment impact the metabolic changes that are required to maintain 
their malignant state. Project 2 focuses on a key outcome of these metabolic changes, specifically, the 
generation of microvesicles (MVs), a class of extracellular shed vesicles that are shed from the plasma 
membranes of cancer cells. MVs are receiving increasing attention because of their roles in various 
aspects of cancer progression, including the induction of changes within the tumor microenvironment, the 
stimulation of tumor angiogenesis, and contributions to the metastatic process. However, although we 
understand some of the biochemical signals that trigger MV production, we know little about the physical 
determinants that drive their formation along cancer cell surfaces, nor about how the physical 
microenvironment influences their biogenesis, and ultimately their functions. We intend to probe these 
important issues in Project 2, through three lines of experimental inquiry. 1) Determine the physical 
relationships governing MV biogenesis and size distribution. We will examine the physical changes in 
membrane shape and protein-protein interactions that result in membrane curvature and the maturation of 
MVs. In particular, we will take advantage of our recent discovery that glycans (e.g. Mucin 1), which are 
highly expressed in cancer cells, have a key role in MV biogenesis. 2) Determine the reciprocal 
relationship between the physical properties of the extracellular matrix and MV formation. While 
the vast majority of studies on cancer cell metabolism have been performed in 2D cell culture settings, we 
will explore how the physical features of the 3D microenvironment influence the metabolic cues that drive 
MV biogenesis. 3) Establish physical read-outs such as vesicle size as indicators of MV function in 
tumor-stroma and reciprocal stroma-tumor vesicle transfer. We will implement the necessary 
engineering platforms to isolate MVs from other classes of vesicles in order to eliminate the ambiguity that 
often exists regarding studies using heterogeneous extracellular vesicle preparations and thereby define 
more precisely the functions of MVs. We will determine the effects of MVs on surrounding non-cancerous 
cells (adipose stromal cells and endothelial cells), and examine whether this leads to the production of 
new MVs (e.g. from adipose stromal cells) that might feed-back regulate the metabolism and invasiveness 
of tumor cells. These studies will take advantage of the two PSOC Cores, Tissue Microfabrication and 
Biophysics and Metabolic Imaging, and will complement and benefit from Projects 1 and 3. 
Collectively, they will shed new light on cancer cell metabolism and how it gives rise to MV biogenesis, 
with the expectation being that ultimately novel therapeutic strategies will emerge from ...

## Key facts

- **NIH application ID:** 10020780
- **Project number:** 5U54CA210184-05
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** RICHARD A. CERIONE
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,556
- **Award type:** 5
- **Project period:** — → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020780

## Citation

> US National Institutes of Health, RePORTER application 10020780, Project 2: Metabolism-Mediated Changes of Microvesicle Biogenesis (5U54CA210184-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10020780. Licensed CC0.

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