# Oncogenic Synapses: cell-cell contacts enabling trogocytic-based metabolic interactions between pancreatic cancer and fibroblastic stromal cells

> **NIH NIH R21** · RESEARCH INST OF FOX CHASE CAN CTR · 2020 · $200,481

## Abstract

PROJECT SUMMARY/ABSTRACT
The project titled “Oncogenic Synapses: cell-cell contacts enabling trogocytic-based metabolic
interactions between pancreatic cancer and fibroblastic stromal cells” directly addresses the NCI
Provocative Question (PQ) #7 in seeking advancement in understanding of the pathognomonic significance and
functions of newly described synapse-like heterotypic cell-cell contacts formed between carcinoma cells and
cancer-associated fibroblasts (CAFs). CAFs are known to provide cancer cells with nutrients and reciprocally-
induced signaling inputs. Pancreatic cancer (PC), particularly pancreatic ductal adenocarcinoma, is an extreme
example of preponderance of stroma in which particular CAF characteristics confer negative prognosis. Our
combined and highly complementary preliminary findings serve as a basis to study the previously
uncharacterized heterotypic cell-cell “oncogenic synapse” structure and its PC supportive function. Two specific
aims will test the hypothesis that PC cells depend on NTNG1-NGL1 engagement to form oncogenic synapses
and consume cholesterol via Wnt5a-regulated Ca2+ and phosphatidylserine (PtdSer)-dependent trogocytosis.
Aim 1 will define the molecular requirements for NTNG1-NGL1 engagement and functional oncogenic synapse
formation. Molecular engineering of NTNG1 and NGL1 proteins and microscopy imaging will define the structural
and functional particulars of the oncogenic synapses formed between CAF and PC cells.
Aim 2 will determine the importance of NTNG1/NGL1-mediated oncogenic synapses in trogocytosis. Based on
preliminary experiments, we will test if NTNG1-NGL1 engagement is needed for the PC cell-executed
trogocytosis.
The cell-cell contact structures involved in the CAF-PC oncogenic synapses that facilitate trogocytosis have not
been previously described. Therefore, their detailed molecular and cell biology characterization is critical. The
adaptation of neuronal synapse mechanisms by PC cells bypasses the metabolic restrictions imposed by the
PC microenvironment. Thus, the oncogenic synapses may be the key to understanding the direct CAF-PC cell-
cell communication which endorses malignant progression.

## Key facts

- **NIH application ID:** 9894770
- **Project number:** 5R21CA231252-02
- **Recipient organization:** RESEARCH INST OF FOX CHASE CAN CTR
- **Principal Investigator:** Igor Astsaturov
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,481
- **Award type:** 5
- **Project period:** 2019-03-15 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894770

## Citation

> US National Institutes of Health, RePORTER application 9894770, Oncogenic Synapses: cell-cell contacts enabling trogocytic-based metabolic interactions between pancreatic cancer and fibroblastic stromal cells (5R21CA231252-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894770. Licensed CC0.

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