Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers learn why PSA levels reflect prostate cancer progression

14.01.2011
Researchers at the Duke Cancer Institute who have been studying prostate cancer cells for decades now think they know why PSA (prostate-specific antigen) levels reflect cancer progression.

"This is the first demonstration of a mechanism that explains why PSA is a bad thing for a tumor to produce," said senior author Sal Pizzo, M.D., Ph.D., chair of the Duke Department of Pathology. "I am willing to bet there is also a connection in cancerous cell growth with this particular biological signaling mechanism happening in other types of cells."

Using human prostate cancer cells in a laboratory culture, the team found that an antibody reacts with a cell surface receptor called GRP78 on the cancer cells to produce more PSA. The PSA arises inside of the cancer cell and then moves outside of the cell, where it can bind with the same antibody, called alpha2-macroglobulin (á2M).

The PSA forms a complex with the antibody that also binds to the GRP78 receptor, and that activates several key pathways which stimulate cancer cell growth and cell movement and block cell death.

The study bolsters the case for measuring PSA as a marker of tumor progression, as well as for monitoring for á2M antibody levels.

"The use of PSA to make the initial diagnosis of prostate cancer has become controversial over the past decade," Pizzo said. "I personally believe PSA is more useful as a progression marker, particularly with a baseline value on record at the time of the original therapy. A rapidly rising value and/or a very high value is reason for concern. I also believe that monitoring the serum for the appearance of antibodies directed against GRP78 is also a good marker of progression."

Pizzo said that the findings could yield cancer therapies that block the á2M-PSA complex from stimulating the cell receptor signaling cascade, and that his laboratory is investigating possibilities. He said the findings also might yield new kinds of early-detection tests for prostate cancer.

The study will be published in the Jan. 14 edition of the Journal of Biological Chemistry.

Pizzo credits lead author and signaling pathway expert, biochemist Uma Misra, Ph.D., with deducing that PSA may be involved in a signaling feedback loop that promotes more aggressive behavior in the human prostate cancer cells.

"If you were a cancer cell, you would like to turn on cell growth, turn off the process of death by cell apoptosis and you'd like to be able to migrate, and when the á2M antibody binds with the protease PSA molecule, all of that happens," Pizzo said.

Years ago, Misra discovered the GRP78 receptor on the prostate tumor cell surface, the receptor that binds the á2M antibody and the á2M-PSA complex.

"We were surprised to find that this complex binds with the protein GRP78, because we thought the GRP78 molecule only lived deep inside the cell, where it was busy taking improperly folded proteins and helping them to fold properly," Pizzo said. "It was a surprise to find GRP78 on the cell surface, with other functions. Based on the dogma of the time, we didn't think that GRP78 could function as a receptor. Even when we identified it, I doubted our findings."

Pizzo said that since Misra first made the observation about GRP78 working as a receptor, "it has turned into a cottage industry. GRP78 receptors have been discovered on many other cancer cells, including breast, ovary, liver, colon, melanoma and lung cancer cells."

"This is going to be a generic phenomenon to tumors," predicted Pizzo, who is also working to learn more about this receptor in other types of cancer cells. "Not all tumors will express GRP78 on their cell surfaces, but when they do, it probably will be a harbinger of a bad outcome."

"I think we will find that nature favors conservation and it makes sense that the body uses the same types of molecules for different purposes," Pizzo said. "We are beginning to see more of this in other studies, and I predict we will see many more instances."

The other co-author on this paper is Sturgis Payne, also of the Duke Department of Pathology. Funding for the current study came from a small fund from the Duke Department of Pathology.

Mary Jane Gore | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>