Human cells with `built-in circuit` can kill cancer cells

London: 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.

"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.

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. 

"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.