# Imaging mass spectrometry methodologies for studying the metabolites of cancer metastasis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $376,650

## Abstract

High grade serous ovarian cancer (HGSC) is the most common and deadliest form of ovarian cancer.
Emerging evidence indicates that these tumors arise in the fallopian tube epithelium (FTE), and thus their
presence in the ovary represents the primary metastasis. Our preliminary data identified that xenografting in
close proximity to the ovary contributes to the aggressiveness of the disease. After ovarian colonization, tumor
cells invade the peritoneal organs, primarily the omentum. We hypothesize that the biological problem of
primary and secondary HGSC metastasis is partially mediated by chemical communication between
the cancer cells and the metastatic organ. Our proposal seeks to define metabolites and biomolecules that
drive the metastasis of fallopian tube derived high grade serous cancers to the ovary and the omentum. To this
end, our teams optimized a 3D co-culture of the ovary and fallopian tube derived tumor models and adapted
this to imaging mass spectrometry technology to identify the metabolomics-driven communication that occurs
during primary colonization of the ovary and during secondary metastasis to the omentum. Using this emerging
technology, we identified several metabolites that enhanced high grade serous tumor migration, invasion, and
adhesion to the ovary. The focus of Aim 1 is to uncover the mechanisms allowing FTE tumorigenic cells to
hijack NE produced by the ovary to increase their ability to invade and adhere to the ovary during primary
metastasis. Aim 1 will define the signaling pathways mediated by NE during invasion and adhesion to the
ovary and then confirm the importance of NE in vivo using both murine and human cell models derived from
FTE. The key adrenergic receptor will be deleted using CRISPR to confirm the importance of this pathway in
metastasis. Tumor bearing models will be treated with beta adrenergic receptor antagonists in an attempt to
translate these findings for a new strategy to block ovarian colonization. The focus of Aim 2 is on the
identification and characterization of a newly identified protein that is secreted from tumorigenic fallopian tube
cells and is responsible for the production of ovarian norepinephrine driving tumor cell invasion and adhesion.
We will use proteomics to confirm the identity of the secreted protein, followed by genetic deletion of the
protein from FTE models to study the role in ovarian colonization. Aim 3 will build upon our existing technology
of 3D organ and tumor cell communication models and expand into secondary metastasis. We have now
optimized our technology for co-culture of the omentum together with tumor cell models and have an inventory
of metabolites, which are unique and did not include norepinephrine. Instead a novel metabolite found to be
produced in significantly more abundance when tumor cells were grown with the omentum corresponded to
folate, the ligand for the folic acid receptor that is overexpressed in the tumor cells. Taken together, our
innovative e...

## Key facts

- **NIH application ID:** 9970786
- **Project number:** 1R01CA240423-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Joanna E Burdette
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,650
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970786

## Citation

> US National Institutes of Health, RePORTER application 9970786, Imaging mass spectrometry methodologies for studying the metabolites of cancer metastasis (1R01CA240423-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9970786. Licensed CC0.

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