# Project 2: Fetuin-A in Prostate Cancer

> **NIH NIH U54** · TENNESSEE STATE UNIVERSITY · 2024 · $64,280

## Abstract

PROJECT SUMMARY: FULL PROJECT 2
Even though the growth of prostate cancer (PCa) is largely driven by androgens, a subset usually develops that
is refractory to androgen ablation (also known as castration resistant PCa; CRPC) with potential for metastasis.
Preliminary data from our laboratory has implicated fetuin-A, also known as alpha 2-Heremans-Schmid
glycoprotein (AHSG), in the growth of PCa cells and in the production of “uptake-competent” exosomes. The
objective of the proposed studies is to define the role and significance of fetuin-A in prostate cancer progression.
We hypothesize that PCa cells express ectopic fetuin-A which is secreted and taken up by the cells via TLR4 to
mediate the biogenesis of `uptake-competent' exosomes that promote PCa growth via activation of pAKT/pERK;
moreover, we postulate that elevated fetuin-A expression serves as a prognostic biomarker for PCa. Three
specific aims are proposed: Aim 1. To determine if fetuin-A expression is higher in AA PCa tissues relative
to Caucasian American (CA) PCa tissues and whether high fetuin-A expression is associated with high
Gleason Scores (>6) and enhanced pAKT and pERK. We will analyze mRNA expression of fetuin-A using
NanoString as well as pAKT/pERK protein levels using immunohistochemistry (IHC) analysis of human PCa
tissues. Multivariable linear regression analysis will be used to determine the correlation between fetuin-A, pAKT,
pERK and Gleason scores in PCa tissues of AA and CA patients, as well as other progression parameters such
as positive margins and spread of PCa. It is expected that fetuin-A, pAKT and pERK will be expressed at high
levels in PCa tissues of AA patients particularly those with high Gleason scores (>6). Aim 2. To determine the
role of ectopic fetuin-A in exosome biogenesis, promotion of 2-D and 3-D growth, motility and invasive
capacity of PCa cells. In this aim, we will overexpress and knockout fetuin-A in two PCa cell lines to determine
whether fetuin-A plays a causal role in the biogenesis of `uptake competent' exosomes that transmit growth
signals in recipient cells. We expect to demonstrate that exosomes from fetuin-A overexpressing cells will
promote 2-D, 3-D growth and motility and invasion of PCa cells while exosomes from fetuin-A null cells will not.
Aim 3. To investigate the efficacy of targeting fetuin-A mediated signaling on the suppression of prostate
tumor initiation and growth in mice. In this aim, we will utilize the Pten-null mouse model for PCa to determine
whether Pten loss requires intact fetuin-A gene to mediate its tumorigenic role and whether loss of fetuin-A in
Pten-/-/fetuin-A-/- double mutant mice attenuates the tumorigenic role of Pten-null. We expect reduced tumor
growth in the double mutant mice compared to Pten-null fetuin-A+/+ mice. Significance: There is an urgent need
to identify biomarkers that can differentiate CRPC from indolent PCa and this proposal addresses that need and
evaluates the process by which fetuin-A e...

## Key facts

- **NIH application ID:** 10908459
- **Project number:** 5U54CA163066-14
- **Recipient organization:** TENNESSEE STATE UNIVERSITY
- **Principal Investigator:** Xiaofei Wang
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $64,280
- **Award type:** 5
- **Project period:** 2011-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908459

## Citation

> US National Institutes of Health, RePORTER application 10908459, Project 2: Fetuin-A in Prostate Cancer (5U54CA163066-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10908459. Licensed CC0.

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