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Nemours Center for Childhood Cancer Research Team at the Alfred I. duPont Hospital for Children Identifies the Function of a Biomarker Present in Prostate Cancer Cells: New Insight into Therapeutic Benefit for Patients with Advanced Prostate Cancer
WILMINGTON, Del., July 17 /PRNewswire/ -- The research team at the Nemours
Center for Childhood Cancer Research (NCCCR), a newly established division of
Nemours Biomedical Research at the Alfred I. duPont Hospital for Children has
discovered that the biomarker called prostate specific membrane antigen
(PSMA), abundantly present in cancer cells of patients with advanced prostate
cancer, has a contributory role in the progression of cancer to an aggressive
disease. A biomarker is any biomolecule that is associated with a particular
pathological or physiological state of cells and may be used to diagnose and
treat a disease or monitor response to therapy.
The discovery, titled "Prostate specific membrane antigen associates with
anaphase promoting complex and induces chromosomal instability," is outlined
in the July issue of Molecular Cancer Therapeutics, an American Association
for Cancer Research journal and provides new insights into therapeutic benefit
for patients with advanced prostate cancer.
The research was conducted by Dr. Ayyappan K. Rajasekaran, the Director of
NCCCR, and his research team while they were at the University of California,
Los Angeles, and at NCCCR. The abundance of PSMA in prostate cancer cells
increases as the cancer progresses into a metastatic and hormone-independent
advanced disease. Dr. Rajasekaran said, "We strongly suspected that PSMA has
a potential role in the progression of prostate cancer into an aggressive
disease. But how it participates in disease progression was not clear. Now in
this study, we identified that PSMA does have an important causative role in
prostate cancer progression."
This study was initiated when the researchers found that PSMA was present
at the poles of the dividing cells. These poles are complex structures at the
opposite ends of the cells that control the separation of chromosomes equally
into daughter cells during cell division. "Presence of PSMA at the poles
indicated it might have a role in cell division and chromosome segregation,
and we continued our quest to understand this potential function of PSMA,"
said Dr. Rajasekaran.
Human cells have 46 chromosomes. The chromosomes are vehicles that carry
the genetic material DNA from generation to generation. These chromosomes are
equally divided into daughter cells during cell division. Cells have several
checkpoints to ensure that the chromosomes are equally separated during cell
division. Anaphase-promoting complex (APC) is one such checkpoint regulatory
protein involved in the proper segregation of chromosomes during cell
division. This complex monitors the timing of cell division and provides
sufficient time for cells to segregate chromosomes equally into daughter
cells. Often, cancer cells have more than 46 chromosomes, a condition known as
aneuploidy, which is a constant feature of aggressive, advanced, and
drug-resistant solid tumors, including prostate cancer.
Rajasekaran and his research team found that PSMA-expressing cells spent
less time dividing. They found that PSMA interferes with the function of APC
and induces aneuploidy in cancer cells. "When PSMA is present, cells hurried
to complete their division prior to having all their chromosomes properly
segregated," said Dr. Sigrid A. Rajasekaran, the first author of the study and
the head of the Cancer Cell Metabolism Laboratory at NCCCR.
PSMA is present in prostate cancer cells but not in normal cells.
Therefore, it is an excellent therapeutic target for prostate cancer. There
are several ongoing clinical trials for PSMA-based therapeutic interventions.
"Since PSMA expression is higher in metastatic compared to benign cancer
cells, anti-PSMA-based therapeutic strategies should target metastatic
prostate cancer cells, which will benefit patients with advanced prostate
cancer," the study states.
Dr. A. Rajasekaran and his team conducted their research on cell lines and
are in the process of translating their findings into human clinical trials,
which should be available in two to three years.
This study was primarily supported by the Department of Defense DOD
W81XWH-04-1-0113 Idea Development Grant and in part by NIH DK56216.
About the Nemours Center for Childhood Cancer Research
The Nemours Center for Childhood Cancer Research is a newly established
research entity of Nemours Biomedical Research at the Alfred I. duPont
hospital for children. The NCCCR is located in a fully renovated laboratory
space in 1701 Rockland Road,Wilmington, DE. The goal of the center is to
evolve into a leader in research focusing on biomarkers for childhood cancers
and cancers that affect families. The NCCCR will closely work together with
Helen F. Graham Cancer Center, University of Delaware, Center for
Translational Research and the Delaware Biotechnology Institute. The Alfred
I. duPont Hospital for Children is a division of Nemours, which operates one
of the nation's largest health systems devoted to pediatric patient care,
teaching, and research. Set on a 300-acre campus nearWilmington, Delaware,
the 200-bed duPont Hospital for Children offers all the specialties of
pediatric medicine, surgery, and dentistry. Starting with Alfred I. duPont's
bequest over 70 years ago, Nemours has grown into a multi-dimensional
organization offering personalized clinical and preventive care focused on
children. For more information, please visit Nemours.org.
SOURCE Nemours Center for Childhood Cancer Research
Copyright © 2008, PRNewswire
Copyright © 2008, NewsBlaze,
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