Navigation Links
UCLA cancer researchers shake loose hidden biomarker

Using a common chemotherapy agent, researchers at UCLA's Jonsson Cancer Center and the Department of Pathology and Laboratory Medicine found a way to move an important biomarker expressed in prostate cancer, shaking it loose from one location in a cell ?where it could not be accessed by blood ?to another, easier to target area.

The discovery, outlined in the cover article of May 11 edition of the peer-reviewed journal Molecular Cancer Therapeutics, could have important implications for using immunotherapy to treat prostate cancer, said Ayyappan K. Rajasekaran, a Jonsson Cancer Center researcher and senior author of the article.

The method discovered by the research team places the prostate-specific membrane antigen (PSMA) in a location on the cell that would allow blood-borne immunotherapies to access the biomarker, transforming it from a hidden target into an exposed one.

"In prostate cancer cells, PSMA is expressed in the apical region of the cell membrane, which blood can't reach, so injection of immunotherapy into the bloodstream is not effective," said Rajasekaran, also an associate professor of pathology and laboratory medicine. "By using information from very basic studies about how the PSMA protein is targeted in these cells, we identified a way to redirect this protein within the cell. We found that if we disturbed hollow tubular structures called microtubules, part of the cell's framework, we were able to relocate PSMA from its 'hidden' location on the apical membrane to an accessible area in the basolateral surface."

To cause this disturbance and the resulting relocation of PSMA, Rajasekaran and his team employed a commonly used cancer chemotherapy agent, which destroys the microtubules.

"These patients are getting chemotherapy anyway, and once we move the PSMA to a more accessible area on the prostate cancer cell, we might be able to use antibody-based immunotherapies as well, and they could be administered in the b lood," he said.

Rajasekaran said PSMA is an important biomarker for prostate cancer and its expression in the cell is proportional to the severity of the cancer ?the more advanced the disease, the more PSMA is expressed.

Rajasekaran and his team also showed for the first time in this study that prostate cancer cells maintain a well-differentiated morphology, with the PSMA hidden in the apical membrane of the cell, even when the cancer spreads outside the prostate ?a fact that hadn't been proven before. Many researchers, in fact, had believed the opposite was true, Rajasekaran said. So discovering the mechanism of moving the PSMA to a more treatment accessible location on the cell could have ramifications for treating the sickest patients, those in whom the cancer has spread.

"The ability to reverse the polarity of PSMA from apical to the basolateral could have significant implications for the PSMA as a therapeutic target," the study states.

Pairing treatments may be even more important for patients with advanced cancers, for whom few options are available, Rajasekaran said. "Chemotherapy alone doesn't do everything and immunotherapy alone might not do everything, but if could use both, we might have more success in treating patients, especially those whose cancer has spread," he said.

Rajasekaran and his team performed their research in prostate cancer cells lines and plan to validate their findings first in animal models and then in human clinical trials, which could be available in three to four years.

Prostate cancer is expected to strike 232,090 men this year alone, according to the American Cancer Society. Of those, 30,350 are expected to die. Prostate cancer is the second leading cause of cancer death in men.


Source:University of California - Los Angeles

Related biology news :

1. Viral DNA sequence a possible trigger for breast cancer
2. Enzyme, lost in most mammals, is shown to protect against UV-induced skin cancer
3. Its not all genetic: Common epigenetic problem doubles cancer risk in mice
4. Columbia research lifts major hurdle to gene therapy for cancer
5. Combination therapy boosts effectiveness of telomere-directed cancer cell death
6. Mitochondrial DNA mutations play significant role in prostate cancer
7. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
8. BRCA1 causes ovarian cancer through indirect, biochemical route
9. Researchers identify target for cancer drugs
10. Weizmann Institute scientists develop a new approach for directing treatment to metastasized prostate cancer in the bones.
11. First atlas of key brain genes could speed research on cancer, neurological diseases
Post Your Comments:

(Date:5/20/2016)...  VoiceIt is excited to announce its new ... By working together, VoiceIt and VoicePass will offer ... take slightly different approaches to voice biometrics, collaboration ... usability. Both ... "This marketing and technology partnership allows ...
(Date:5/3/2016)... 3, 2016  Neurotechnology, a provider of high-precision ... Automated Biometric Identification System (ABIS) , a complete ... MegaMatcher ABIS can process multiple complex biometric transactions ... of fingerprint, face or iris biometrics. It leverages ... and MegaMatcher Accelerator , which have been ...
(Date:4/26/2016)... Research and Markets has announced ... 2016-2020"  report to their offering.  , ,     (Logo: ... analysts forecast the global multimodal biometrics market to ... period 2016-2020.  Multimodal biometrics is being ... the healthcare, BFSI, transportation, automotive, and government for ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... , June 27, 2016 /PRNewswire/ - BIOREM Inc. (TSX-V: BRM) ... advised by its major shareholders, Clean Technology Fund I, ... United States based venture capital funds which ... Biorem (on a fully diluted, as converted basis), that ... of their entire equity holdings in Biorem to TUS ...
(Date:6/27/2016)... ... ... Parallel 6 , the leading software as a service (SaaS) provider ... Patient Encounter CONSULT module which enables both audio and video telemedicine communication between the ... the CONSULT module, patients and physicians can schedule a face to face virtual patient ...
(Date:6/27/2016)... -- Liquid Biotech USA , Inc. ... Research Agreement with The University of Pennsylvania ("PENN") ... patients.  The funding will be used to assess ... outcomes in cancer patients undergoing a variety of ... to support the design of a therapeutic, decision-making ...
(Date:6/24/2016)... , June 24, 2016 Epic Sciences ... detects cancers susceptible to PARP inhibitors by targeting ... cells (CTCs). The new test has already been ... in multiple cancer types. Over 230 ... damage response pathways, including PARP, ATM, ATR, DNA-PK ...
Breaking Biology Technology: