# Development of quantitative mass spectrometry assays and imaging for cancer metastasis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $85,846

## Abstract

Parent award 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 tog...

## Key facts

- **NIH application ID:** 10533035
- **Project number:** 3R01CA240423-03S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Joanna E Burdette
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $85,846
- **Award type:** 3
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10533035

## Citation

> US National Institutes of Health, RePORTER application 10533035, Development of quantitative mass spectrometry assays and imaging for cancer metastasis (3R01CA240423-03S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10533035. Licensed CC0.

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