# Mechanistic Insights and Diagnostic Applications for Hypoxia-Induced Vasorin in Pancreatic Cancer

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $41,081

## Abstract

Project Summary
With the advent of cancer immunotherapies, patients have seen dramatic increases in the availability of
treatment options for various malignancies. However, many of these modalities lack efficacy in treating solid
tumors, namely because of the unique set of environmental factors that exist within these tumors. One of the
most ubiquitous features within the tumor microenvironment (TME) is oxygen deprivation, also known as
hypoxia. Hypoxia has long been linked to increased metastasis and poorer prognoses for patients. In response
to hypoxic stress, cancer cells activate highly regulated cellular pathways and gene programs that promote
survival, migration, immune privilege, and increased mortality for patients. Across all solid tumors, pancreatic
cancer exhibits the most severe hypoxic phenotype, which may contribute to the high mortality rate associated
with this cancer type. These hypoxia-specific downstream effects suggest that tumor hypoxia can be used to
elucidate selective biomarkers of solid pancreatic cancer for diagnostic and therapeutic purposes. Here, I utilize
cell surface proteomics to identify a novel hypoxia-regulated target in pancreatic cancer called vasorin (VASN),
a target previously implicated in the progression of glioblastoma. Furthermore, I have shown that VASN plays
an important role in the growth and survival of pancreatic cancer under hypoxic stress. Finally, I have isolated
and expressed ten unique antibody clones against the ectodomain of VASN. Using these antibodies, I found that
VASN undergoes numerous cleavage events under hypoxia in vitro, which are unique from previously published
results. We hypothesize that VASN cleavage is necessary for the survival and proliferation of pancreatic cancer
under hypoxia, and that classification of expression levels for cleavage-specific forms of VASN in relevant tumor
models will aid the downstream development of antibody-based diagnostics for hypoxic pancreatic cancer. To
test this hypothesis, I will employ proteomic characterization and recombinant protein expression to identify the
in vitro cellular consequences of VASN proteolysis. In order to isolate clones towards the membrane-retained
form of cleaved VASN, I will use an established phage display-based recombinant antibody strategy. A selective
antibody-based biotinylation strategy will be implemented to identify novel interacting partners of the membrane-
retained form of cleaved VASN that may play an important role in downstream signaling. Finally, I will
functionalize my existing and future anti-VASN antibody clones for serum-based ELISA detection and
radiotracer-based immunoPET imaging of VASN, respectively, which will validate the presence of proteolyzed
VASN in human serum and tumors, as well as in an in vivo nu/nu mouse model of pancreatic cancer. The
proposed studies will provide mechanistic insights into the functional consequences of VASN proteolysis in
pancreatic cancer, as well as providing evidence...

## Key facts

- **NIH application ID:** 10088332
- **Project number:** 5F31CA247527-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Lisa Kirkemo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $41,081
- **Award type:** 5
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088332

## Citation

> US National Institutes of Health, RePORTER application 10088332, Mechanistic Insights and Diagnostic Applications for Hypoxia-Induced Vasorin in Pancreatic Cancer (5F31CA247527-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10088332. Licensed CC0.

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