# Role of Ferroportin in reducing Prostate Cancer Metastasis

> **NIH NIH F30** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $51,320

## Abstract

Abstract:
 Prostate cancer patients diagnosed with late-stage, distant-metastatic disease have a dismal 28% 5-
year survival rate; particularly in contrast to the 100% 5-year survival rate of local and regional disease.
Considering the fact that prostate cancer is the most common cancer among men in the United States, and the
second most common worldwide, effective therapies for treating metastatic prostate cancer remains a
significant unmet clinical need. This proposal aims to identify a novel therapeutic target to treat metastatic
prostate cancer by elucidating the role of ferroportin, the only known iron export protein in mammals, in the
metastatic spread of prostate cancer.
 Ferroportin is the only known iron export protein in vertebrates and is a key mechanism for regulating
cellular and systemic iron levels. This protein is part of a regulatory axis, with its negative regulator hepcidin,
that controls iron levels. This regulatory axis is disturbed in cancer cells which exhibit elevated iron levels,
reduced ferroportin levels, and increased hepcidin relative to normal tissue. Emerging evidence suggests that
iron plays a critical role in metastatic processes. Through regulation of iron, so too may ferroportin. Analysis of
patient samples does indeed indicate that ferroportin is differentially regulated in normal, primary tumor tissue,
and metastatic tumor tissue. This proposal investigates mechanisms by which ferroportin expression may
regulate the metastatic spread of prostate cancer. Aim 1 tests the hypothesis that ferroportin expression
regulates cellular motility and invasiveness. Motility is studied phenotypically by gap closure assays and
transwell motility assays. Invasion is assessed by transwell invasion assays. Potential mechanisms include the
iron-regulated metastasis suppressor N-myc downstream regulated gene-1 (NDRG1), matrix
metalloproteinases and serine proteinases. Aim 2 tests the hypothesis that ferroportin regulates cancer cell
viability at the metastatic site. NDRG1 and cell cycle regulators p21 and p38 are investigated as mechanisms.
The phenotype of ferroportin overexpression will be assessed in vivo by evaluation of intratibial tumor growth,
development of bone lesions, and by proliferative markers.

## Key facts

- **NIH application ID:** 10074136
- **Project number:** 5F30DE026380-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** David H Manz
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $51,320
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074136

## Citation

> US National Institutes of Health, RePORTER application 10074136, Role of Ferroportin in reducing Prostate Cancer Metastasis (5F30DE026380-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074136. Licensed CC0.

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