Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Protein found in heart may be target for colon cancer therapies

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."

The research was supported by grants from the National Institute of Diabetes and Digestive and Kidney Disorders, National Cancer Institute, National Center for Research Resources, National Institute of General Medical Sciences, and the National Eye Institute.

Melissa Marino | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Inflammation Triggers Unsustainable Immune Response to Chronic Viral Infection
24.10.2016 | Universität Basel

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>