# Mechanism behind CCL21/CCR7-mediated pancreatic cancer progression

> **NIH NIH F30** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $46,324

## Abstract

PROJECT SUMMARY
 Pancreatic cancer is a devastating disease with incredibly low survival rates, especially for those who
present with metastases at the time of diagnosis. Unfortunately, surgery and combination chemotherapies
have not made significant advances in survival. As such, novel approaches to therapy are desperately needed.
Since metastases, and specifically lymph node metastases, are often responsible for recurrence and poor
prognosis, elucidating the mechanism behind metastasis can provide invaluable information and a new
therapeutic target in pancreatic cancer.
 The process of metastasis involves the migration of tumor cells to new sites. Chemokines normally
direct the migration of cells from one tissue to another. This process can be hijacked by tumor cells, allowing
metastasis to lymph nodes and distant sites. The chemokine ligand-receptor pair, CCL21 and CCR7, direct the
traffic of immune cells towards the lymph nodes. CCR7 has increased expression in many cancers and has
been associated with lymph node metastasis and worse prognosis. Interestingly, CCL21 is structurally unique
due to a long C-terminal tail that may be inhibiting its interaction with its receptor CCR7 in an autoinhibitory
fashion. Furthermore, the post-translational modification polysialic acid, shown separately to correlate with
metastasis, has been implicated as the agent that relieves CCL21's autoinhibition. Together, these three
components, CCR7, CCL21, and polysialic acid, each separately implicated in cancer metastasis, are
combined to form the basis of this proposal.
 The goal of this fellowship is to test the hypothesis that polysialylated CCR7 binding to CCL21 mediates
lymph node metastasis in pancreatic cancer. The pursuit of this goal will be accomplished through two aims.
Aim 1 will employ NMR spectroscopy to delve into the mechanism of autoinhibition by examining the structural
interactions between polysialic acid on CCR7 and the C-terminus of CCL21. Aim 2 will use a combination of
signaling and migration assays, in addition to in vivo animal studies, to study the functional role of these
players in lymph node metastasis in pancreatic cancer. Exploiting the complementary relationship between
structure and function through completion of these two aims will provide details on a novel mechanism that can
be targeted to develop therapeutics against this highly aggressive disease.

## Key facts

- **NIH application ID:** 9968156
- **Project number:** 5F30CA210587-05
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Natasha A Moussouras
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $46,324
- **Award type:** 5
- **Project period:** 2016-07-01 → 2021-06-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968156

## Citation

> US National Institutes of Health, RePORTER application 9968156, Mechanism behind CCL21/CCR7-mediated pancreatic cancer progression (5F30CA210587-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9968156. Licensed CC0.

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