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Human Cells with ‘Built-in Genetic Circuit’ can impair ability of Cancer Cells to Survive and Grow, say Researchers

As tumours develop and grow, they rapidly outstrip the supply of oxygen delivered by existing blood vessels

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FILE - A biotechnician demonstrates the loading of a genome sequencing machine at the J. Craig Venter Institute in Rockville, Maryland. Relative to their ability to pay, cancer patients in China and India face much higher prices than wealthier U.S. patients. VOA

London, Nov 26, 2016: Researchers have engineered cells with a “built-in genetic circuit” that produces a molecule that impairs the ability of cancer cells to survive and grow in their low oxygen environment.

The genetic circuit produces the machinery necessary for the production of a compound that inhibits a protein which has a significant and critical role in the growth and survival of tumours.

This results in the cancer cells being unable to survive in the low oxygen, low nutrient tumour micro-environment.

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“In a wider sense, we have given these engineered cells the ability to fight back — to stop a key protein from functioning in cancer cells,” said lead researcher Ali Tavassoli, Professor at the University of Southampton in Britain.

“This opens up the possibility for the production and use of sentinel circuits, which produce other bioactive compounds in response to environmental or cellular changes, to target a range of diseases including cancer,” Tavassoli said.

As tumours develop and grow, they rapidly outstrip the supply of oxygen delivered by existing blood vessels. This results in cancer cells needing to adapt to a low oxygen environment.

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To enable them to survive, adapt and grow in the low oxygen or ‘hypoxic’ environment, tumours contain increased levels of a protein called Hypoxia-inducible factor 1 (HIF-1).

This protein senses reduced oxygen levels and triggers many changes in cellular function, including a changed metabolism and sending signals for the formation of new blood vessels.

It is thought that tumours primarily hijack the function of this protein (HIF-1) to survive and grow.

“In an effort to better understand the role of HIF-1 in cancer, and to demonstrate the potential for inhibiting this protein in cancer therapy, we engineered a human cell line with an additional genetic circuit that produces the HIF-1 inhibiting molecule when placed in a hypoxic environment,” Tavassoli explained.

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“We’ve been able to show that the engineered cells produce the HIF-1 inhibitor, and this molecule goes on to inhibit HIF-1 function in cells, limiting the ability of these cells to survive and grow in a nutrient-limited environment as expected,” Tavassoli noted.

The genetic circuit was incorporated onto the chromosome of a human cell line, which encodes the protein machinery required for the production of their cyclic peptide HIF-1 inhibitor.

The research, published in the journal ACS Synthetic Biology, demonstrates the possibility of adding new machinery to human cells to enable them to make therapeutic agents in response to disease signals. (IANS)

Next Story

New Robotic Tool to Detect, Kill Cancer Cells

In the later-stage cells, the stiffening response is not as strong as they are in the early stage, though both are seemingly similar, the researchers said

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Cancer
Cancer Ribbon. Pixabay

Canadian scientists have developed a kind of magnetic tweezer that can precisely insert a minuscule bead robot into a live human cancer cell, pointing to a new option for diagnosing and killing cancer.

The study, published in the journal Science Robotics, described the design in which a magnetic iron bead about 100 times smaller than the thickness of a human hair can be coaxed into any desired position within the cell, the Xinhua reported.

The bead, about 700 nanometres in diameter, is placed on the microscope coverslip surrounded by six magnetic coils in different planes, and the cancer cell can swallow the bead into its membrane.

Then, the researchers from University of Toronto controlled the bead’s position under a microscope, using a computer-controlled algorithm to vary the electrical current through coils and shaping the magnetic field in three dimensions.

The researchers used their robotic system to study early-stage and later-stage bladder cancer cells. Previously, they had to extract the cell nuclei to examine it.

The team measured cell nuclei in intact cells instead of breaking apart the cell membrane, showing that the nucleus is not equally stiff in all directions.

The reason for increased bleeding is not known. It may be because rivaroxaban is more 'potent', the paper published in the Journal of Clinical Oncology said. (IANS)
Representational image. Pixabay

“It’s a bit like a football in shape. Mechanically, it’s stiffer along one axis than the other,” said Professor Sun Yu.

“We wouldn’t have known that without this new technique.”

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They were able to measure how much stiffer the nucleus got when prodded repeatedly, and thus find out which cell protein or proteins might play a role in controlling this response, which could work as a new method of detecting cancer in early stage.

In the later-stage cells, the stiffening response is not as strong as they are in the early stage, though both are seemingly similar, the researchers said.

Also, the team visualised using the tiny robots to either starve a tumour by blocking its blood vessels, or destroy it directly through mechanical ablation, although those applications are still a long way from clinical uses. (IANS)