‘Make-or-break’ protein holds key to cancer spread

A potential cancer cell extruding from an epithelium. Courtesy of Selwin Wu, Yap Lab, UQ's Institute for Molecular Bioscience

University of Queensland researchers have discovered a protein in cells that could block the escape route of potentially cancerous cells and stop them spreading to other parts of the body.

A team of biologists, physicists and mathematicians led by Professor Alpha Yap from UQ’s Institute for Molecular Bioscience made the discovery using microscopic imaging and statistical techniques.

“The finding could lead to new targeted treatments for cancer and other diseases,” Professor Yap said.

The researchers revealed and analysed molecular processes that cause potentially cancer-causing cells to escape from epithelial tissues, the layers of cells that cover and protect organs, including skin.

Professor Yap said the team had made important new insights into cancer biology, pinpointing the pathway these cells take to exit the epithelial tissue and investigating how the protein N-WASP can block their escape route.

“Abnormal or dying cells pose a risk to the health of the protective barrier that cells form around our organs,” he said.

“The normal cells that surround these dangerous cells use the complex process of cellular extrusion to push them out of the tissue,” Professor Yap said.

“However, when cancer cells are pushed out, it gives them the opportunity to grow or invade surrounding healthy tissue, which can cause the cancer to spread to other parts of the body and make it harder to control and treat.

“So while our normal cells think they’re doing us a favour by pushing out the bad cells, they’re actually helping the cancer cells to spread,” he said.

Professor Yap said his team had found a way to potentially block the escape routes by inhibiting the protein N-WASP, which regulates the internal skeleton of the cells.

“The pathway that makes or breaks these cells from escaping is regulated by N-WASP,” he said.

“We have found that if we can inhibit N-WASP from functioning, then we can stop these potentially cancerous cells from spreading.”

The study was conducted by researchers from UQ’s Institute for Molecular Bioscience in collaboration with Dr Zoltan Neufeld from UQ’s School of Mathematics and Physics.

The research has been published in the scientific journal Nature Cell Biology and was supported by the National Health and Medical Research Council of Australia, the Australian Research Council, the Kids Cancer Project of The Oncology Children’s Foundation, and The University of Queensland.

Confocal and optical microscopy was performed at the IMB’s ACRF Cancer Biology Imaging Facility, established with the generous support of the Australian Cancer Research Foundation.

The Institute for Molecular Bioscience (IMB) is a research institute of The University of Queensland that aims to improve quality of life by advancing medical genomics, drug discovery and biotechnology.

The UQ School of Mathematics and Physics has an international reputation for cutting-edge research and innovative teaching in mathematics, physics and statistics.

Source link: http://www.uq.edu.au/news/node/112860

Nanostarfruits are pure gold for research

Gold nanoparticles created by the Rice University lab of
Eugene Zubarev take on the shape of starfruit in a chemical
bath with silver nitrate, ascorbic acid and gold chloride.
Photo courtesy Zubarev Lab/Rice University

Rice University lab develops starfruit-shaped nanorods for medical imaging, chemical sensing.

They look like fruit, and indeed the nanoscale stars of new research at Rice University have tasty implications for medical imaging and chemical sensing.

Starfruit-shaped gold nanorods synthesized by chemist Eugene Zubarev and Leonid Vigderman, a graduate student in his lab at Rice’s BioScience Research Collaborative, could nourish applications that rely on surface-enhanced Raman spectroscopy (SERS).

The research appeared online this month in the American Chemical Society journal Langmuir.

The researchers found their particles returned signals 25 times stronger than similar nanorods with smooth surfaces. That may ultimately make it possible to detect very small amounts of such organic molecules as DNA and biomarkers, found in bodily fluids, for particular diseases.

“There’s a great deal of interest in sensing applications,” said Zubarev, an associate professor of chemistry. “SERS takes advantage of the ability of gold to enhance electromagnetic fields locally. Fields will concentrate at specific defects, like the sharp edges of our nanostarfruits, and that could help detect the presence of organic molecules at very low concentration.”

SERS can detect organic molecules by themselves, but the presence of a gold surface greatly enhances the effect, Zubarev said. “If we take the spectrum of organic molecules in solution and compare it to when they are adsorbed on a gold particle, the difference can be millions of times,” he said. The potential to further boost that stronger signal by a factor of 25 is significant, he said.

Seen from the side, the nanostarfruit produced at Rice University take
on the appearance of carambola, or starfruit. The particles are about
55 nanometers wide and 550 nanometers long.
Photo courtesy Zubarev Lab/Rice University

Zubarev and Vigderman grew batches of the star-shaped rods in a chemical bath. They started with seed particles of highly purified gold nanorods with pentagonal cross-sections developed by Zubarev’s lab in 2008 and added them to a mixture of silver nitrate, ascorbic acid and gold chloride.

Over 24 hours, the particles plumped up to 550 nanometers long and 55 nanometers wide, many with pointy ends. The particles take on ridges along their lengths; photographed tip-down with an electron microscope, they look like stacks of star-shaped pillows.

Why the pentagons turn into stars is still a bit of a mystery, Zubarev said, but he was willing to speculate. “For a long time, our group has been interested in size amplification of particles,” he said. “Just add gold chloride and a reducing agent to gold nanoparticles, and they become large enough to be seen with an optical microscope. But in the presence of silver nitrate and bromide ions, things happen differently.”

When Zubarev and Vigderman added a common surfactant, cetyltrimethylammonium bromide (aka CTAB), to the mix, the bromide combined with the silver ions to produce an insoluble salt. “We believe a thin film of silver bromide forms on the side faces of rods and partially blocks them,” Zubarev said.

This in turn slowed down the deposition of gold on those flat surfaces and allowed the nanorods to gather more gold at the pentagon’s points, where they grew into the ridges that gave the rods their star-like cross-section. “Silver bromide is likely to block flat surfaces more efficiently than sharp edges between them,” he said.

The researchers tried replacing silver with other metal ions such as copper, mercury, iron and nickel. All produced relatively smooth nanorods. “Unlike silver, none of these four metals form insoluble bromides, and that may explain why the amplification is highly uniform and leads to particles with smooth surfaces,” he said.

Nanostarfruits begin as gold nanowires with pentagonal cross-sections.
Rice chemist Eugene Zubarev believes silver ions and bromide combine to
form an insoluble salt that retards particle growth along the pentagons’
flat surfaces. Photo courtesy Zubarev Lab/Rice University

The researchers also grew longer nanowires that, along with their optical advantages, may have unique electronic properties. Ongoing experiments with Stephan Link, an assistant professor of chemistry and chemical and biomolecular engineering, will help characterize the starfruit nanowires’ ability to transmit a plasmonic signal. That could be useful for waveguides and other optoelectronic devices.

But the primary area of interest in Zubarev’s lab is biological. “If we can modify the surface roughness such that biological molecules of interest will adsorb selectively on the surface of our rugged nanorods, then we can start looking at very low concentrations of DNA or cancer biomarkers. There are many cancers where the diagnostics depend on the lowest concentration of the biomarker that can be detected.”

The National Science Foundation and Welch Foundation supported the research.

Read the abstract at http://pubs.acs.org/doi/abs/10.1021/la300218z

Source: http://news.rice.edu/2012/03/26/nanostarfruits-are-pure-gold-for-research/