Story URL: http://news.medill.northwestern.edu/chicago/news.aspx?id=220531
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Researchers hope protein bond will 'glue' to cancer cells for early detection

by Andrew Holik
Apr 24, 2013


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Photo Courtesy of Todd Huffman

Researchers hope protein bond they have genetically engineered can detect and extract cancerous blood cells, shown above, so that doctors may be aided in diagnosis

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Chart by Andrew Holik/MEDILL

Data from the American Cancer Society

The most common cancers diagnosed in women in the U.S. The totals include the numbers of people living with the cancer and survivors.  

CTCs_Chart2

Chart by Andrew Holik/MEDILL

Data from the American Cancer Society

The most common cancers diagnosed in men in the U.S.

The totals include the numbers of people living with the cancer and survivors. 

Researchers have replicated a protein bond that could "glue" itself to cancer cells and help with future cancer detection.

Splitting up protein that binds collagen, the most abundant protein in mammals, the researchers identified a "molecular glue" most often found in invasive strains of bacteria. It has a single bond with great stability. After genetically engineering that protein bond, the researchers developed a protein chain with a similar capacity for their detection system.

The bond would be used to find circulating tumor cells, cells that shed from a primary tumor in the early stages of cancer progression and travel through the blood stream to other locations in the body.  Detecting the spread of cancer cells earlier would improve accuracy in diagnoses of cancer treatment, allowing for more aggressive therapies.  

“So it was this unusual chemistry,” said Mark Howarth, lead researcher and biochemist at the University of Oxford. “It was first discovered in this weird bacterial virus that actually forms like chain mail.”

According to the most recent American Cancer Society estimates, some 12,549,000 Americans are living with cancer or are survivors. The society estimates that there will be 66,090 new cases of cancer diagnosed in Illinois alone this year.

Cancer occurs in part when cell communication breaks down, often leading to uncontrolled cell growth. Howarth said he believes this technology can help in screening for circulating tumor cells, living solid tumor cells found at low levels in the bloodstream, thus making them harder to detect than most cells.

“This is basically like a molecular glue,” said Vincent Moy, professor of physiology and biophysics at the University of Miami Miller School of Medicine.  “It helps you tag and deliver things very stably.”

The bonds could be genetically engineered to detect or attack different kinds of cancers.

Moy said he believes the bonds be attached to medicines and antibodies that could go into the cell and promote more cell to cell communication and adhesion.

“It helps you repair communication between cells if they were somehow severed,” Moy said.

One method of extracting cancer cells would be using magnetic beads coated with antibodies, an attachment that previously has lacked sturdiness, said Jacob Fierer, a graduate student on the research team. By using the bond they have formed they are able to have the antibody that is very strong without changing its function.

“What we’re thinking of would be in the test tube forming irreversible links, arranging antibodies, and adding them to a blood sample to screen for cancer,” Howarth said. “If you can take blood samples and look and find tumor cells, you can find a screening method to diagnose and start early treatment.”

For people who already have cancer, he said they could use this advancement to follow how the cancer is changing to understand how the changes may resist therapies.

Howarth said the researchers wanted to use amino acids, compounds in nature that build proteins, to generate the bond formation. He said a challenge has always been finding a protein bond that can enter a cell without coming apart.

Howarth said, through various testing, this bond has unmatched cohesiveness, lasting at neutral and slightly more acidic levels as well as various locations of the cell.

Fierer said the bond formation formed at various extreme temperatures, but most efficiently between 4 and 37 degrees Celsius (39 to 99 degrees Fahrenheit).

He said the bond was stable at temperatures from freezing up to 100 degrees Celsius, the boiling point of water, noteworthy because the proteins could not withstand those temperatures before bonding.

Howarth said initial splitting of protein and peptide and bond reforming took hours, but eventually they were able to speed the formation up to minutes. He said 40 percent of the bonds were forming in under a minute by the end of testing.

Howarth said circulating tumor cell screening has been researched in breast cancer, but he hopes to increase research in other cancer fields.

Moy said the project appears far from being translational, but he said he thinks it has potential to be very useful.

Howarth said there are still a lot of challenges to both the research and treatment. He said the next step is to use this architecture in model systems before it can be tested on human patients.  For one, he said cancer cells are hard to isolate and differ from person to person. He said it will take a lot of precision to find these circulating tumor cells in other cancers.

“We showed that you do need a lot of things right to push the limit,” he said.