Biomedical Tattoo Detects Cancer-Associated Hypercalcemia

A new study describes how a mole-like synthetic implant recognizes the elevated levels of calcium in the blood associated with incipient prostate, lung, colon, and breast cancer tumors.

Developed by researchers at ETH Zurich (Switzerland) and the University of Basel (Switzerland), the so-called early warning system is comprised of an encapsulated gene network integrated into human body cells implanted under the skin, where it constantly monitors blood calcium levels. When calcium levels exceed a pre-determined threshold, a synthetic signaling cascade expresses transgenic tyrosinase, which triggers the production of melanin in the genetically modified cells. The skin then forms a brown mole that is visible to the naked eye.

The researchers validated the design in wild-type mice inoculated with hypercalcemic breast and colon adenocarcinoma cells. The mice, which were implanted with the subcutaneous encapsulated engineered cells, all developed tattoos, whereas no tattoos were seen in animals inoculated with normo-calcemic tumor cells. The study also confirmed that the synthetic biomedical mole could not only be detected with the naked eye, but could also optically quantified. All animals remained asymptomatic throughout the 38-day experimental period. The study was published on April 18, 2018, in Science Translational Medicine.

“It recognizes the four most common types of cancer--prostate, lung, colon, and breast cancer--at a very early stage, namely when the level of calcium in the blood is elevated due to the developing tumor,” said senior author Professor Martin Fussenegger, PhD, of the ETH department of biosystems science and engineering. “An implant carrier should then see a doctor for further evaluation after the mole appears. It is no reason to panic; the mole does not mean that the person is likely to die soon.”

“It is intended primarily for self-monitoring, making it very cost effective. However, for those who would prefer not to deal with the constant stress, an implant can also be used that develops a mark visible only under a red light,” concluded Professor Fussenegger. “The disadvantage is that the service life of such an implant is limited. Encapsulated living cells last for about a year, according to other studies. After that, they must be inactivated and replaced.”

Calcium is an essential element vital to the health of the muscular, circulatory, and digestive systems; is indispensable to the building of bone; and supports synthesis and function of blood cells. For example, it regulates the contraction of muscles, nerve conduction, and the clotting of blood. As a result, intra- and extracellular calcium levels are tightly regulated by the body. Cancer can cause hypercalcemia by bone degradation, releasing excess calcium into the blood; some tumors can produce proteins that mimic parathyroid hormone; and others can affect the ability of the kidneys to remove excess calcium.

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ETH Zurich
University of Basel