Navigation Links
Protein found in heart may be target for colon cancer therapies
Date:9/13/2011

A protein critical in heart development may also play a part in colon cancer progression.

Research led by investigators from Vanderbilt-Ingram Cancer Center and the Vanderbilt Eye Institute suggests that the protein BVES (blood vessel endocardial substance) which also is key in regulating corneal cells may be a therapeutic target for halting colon cancer metastasis.

The study, appearing in the October issue of the Journal of Clinical Investigation, further suggests that BVES may be important more broadly in many, or most, epithelial cancers.

About 85 percent of cancers originate in epithelial cells that form the body's external and internal linings (such as the skin and the lining of the gastrointestinal tract).

However, the main clinical concern is not the primary tumor, but the potential for that tumor to leave its tissue of origin and spread throughout the body (a process called "metastasis").

A critical step in metastatic progression of epithelial cancers happens when epithelial cells "revert" to a less differentiated state a process called "epithelial-mesenchymal transition" or EMT.

Ophthalmologist Min Chang, M.D., studies the healing process in the cornea, perhaps the most highly regulated epithelium in the body. From collaborative studies with David Bader, Ph.D., who discovered BVES and showed its importance in heart development, Chang found that BVES was highly expressed and regulated in corneal cells.

When BVES is disrupted in corneal cells, they become disorganized, almost "cancer-like," noted Chang, an assistant professor of Ophthalmology and Visual Sciences and co-author on the study.

Chang then brought these findings to the attention of colleague Christopher Williams, M.D., Ph.D., assistant professor of Medicine and Cancer Biology and co-author on the study.

"When he described these cells, it sounded a lot like the way cancer cells looked when they were undergoing metastasis," Williams said. "So it seemed reasonable to look in cancer for BVES-dependent phenotypes."

Chang and Williams teamed up with the lab of Daniel Beauchamp, M.D., to assess BVES expression in human colorectal cancers. They found that BVES levels were very low in all stages of colon cancer. They also noted decreased BVES levels in many other types of epithelial cancers (including breast) and in several colorectal cancer cell lines.

To uncover why BVES levels were reduced, the investigators enlisted the help of Wael El-Rifai, M.D., Ph.D., and colleagues. They determined that the BVES promoter (a DNA region that controls gene expression) was heavily modified (methylated), which silenced its expression. In cell experiments, the researchers showed that treating cells with a "demethylating" agent (the drug decitabine, which is currently used to treat myelodysplastic disorders) restored BVES expression. When BVES was expressed in colorectal cancer cell lines, they became more epithelial in nature and their tumor-like characteristics (in cell experiments and in animal models) decreased.

These findings suggest that treatment with agents to increase BVES levels might provide a way to decrease aggressive behaviors of colorectal and other epithelial cancers.

"In cancer, typically the primary tumor doesn't kill you; it's the metastatic disease that proves lethal," said Williams. "So if targeting BVES could interfere with metastasis, that would be very exciting."

The researchers also identified signaling pathways involved in BVES function that may represent other therapeutic targets and that reveal new insights into the normal biological function of BVES. The findings could have implications in wound healing and other normal functions of epithelial cells, as well as for many types of epithelial cancer.

"We don't think it's just isolated to the colon; it pertains to a broad lot of epithelial cancers," Chang noted. "And that's a lot of cancers."


'/>"/>

Contact: Melissa Marino
melissa.marino@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

Related biology news :

1. USC scientists identify key protein linked to acute liver failure
2. Scripps Research scientists pinpoint shape-shifting mechanism critical to protein signaling
3. Scientists find new drug candidates for set of protein-folding diseases
4. Foods rich in protein, dairy products help dieters preserve muscle and lose belly fat: study
5. Research offers new way to target shape-shifting proteins
6. Molecular chaperones traffic signaling proteins between cells in plant stem-cell maintenance pathway
7. Degrading proteins to divide cells
8. Protein in the urine spells kidney failure for African-Americans
9. Single protein, key to ebola virus infection, could aid in drug design
10. Three-part handoff delivers proteins to membrane surface
11. Newfound hijacked proteins linked to salmonella virulence
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/2/2016)... The Department of Transport Management (DOTM) of ... Dollar project, for the , Supply and Delivery ... IT Infrastructure , to Decatur ... Identity Management Solutions. Numerous renowned international vendors participated in the ... was selected for the most compliant and innovative solution. The ...
(Date:6/2/2016)... Perimeter Surveillance & Detection Systems, ... Infrastructure, Support & Other Service  The latest ... comprehensive analysis of the global Border Security market ... of $17.98 billion in 2016. Now: In ... in software and hardware technologies for advanced video surveillance. ...
(Date:5/24/2016)... care by providing unparalleled technology to leaders of the medical imaging industry.  As such, ... to the range of products distributed by Ampronix. Photo - http://photos.prnewswire.com/prnh/20160524/371420 ... ... ... With ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, the Industry Network for ... Design Lab . Located in Pasadena, Calif., the Design Lab’s mission is to ... are designed, built and brought to market. , The Design Lab is Supplyframe’s ...
(Date:6/23/2016)... NC (PRWEB) , ... June 23, 2016 , ... In ... University Hospital in Denmark detail how a patient who developed lymphedema after being treated ... tissue. The results could change the paradigm for dealing with this debilitating, frequent side ...
(Date:6/23/2016)... 23, 2016  Blueprint Bio, a company dedicated to ... medical community, has closed its Series A funding round, ... "We have received a commitment from Forentis ... need to meet our current goals," stated Matthew ... runway to complete validation on the current projects in ...
(Date:6/23/2016)... -- On Wednesday, June 22, 2016, the NASDAQ ... Dow Jones Industrial Average edged 0.27% lower to finish at ... Stock-Callers.com has initiated coverage on the following equities: Infinity Pharmaceuticals ... NKTR ), Aralez Pharmaceuticals Inc. (NASDAQ: ARLZ ... Learn more about these stocks by accessing their free trade ...
Breaking Biology Technology: