Sensor Tracks Zinc in Cells for Prostate Cancer Diagnosis

Mobile zinc is an indispensable component of prostate physiology and the prostate contains more zinc than any other soft tissue in the body, and there is a clear correlation between total prostatic zinc levels and cancer.

A new optical sensor that can track zinc in the body's cells has been described and how the sensor fluoresces when it binds to zinc can be targeted to a specific organelle within a cell, enabling the establishment of where the zinc is most concentrated.

Scientists at the Massachusetts Institute of Technology (Cambridge, MA, USA) developed a sensor that relies on Zinpyr1 (ZP1), a molecule originally developed more than 10 years ago. ZP1 is based on a dye called fluorescein, but in the sensor, this is modified to fluoresce only when it binds with zinc. High-resolution mass spectra were resolved using a mass spectrometer (Bruker Daltonics; Billerica, MA, USA). Fluorescence spectra were recorded on a Quanta Master scanning spectrofluorometer (Photon Technology International; Birmingham, NJ, USA).

The investigators could track the location of zinc within cells and gained a better understanding of the role the mineral plays in cancerous cells. The scientists made two changes to the sensor's design. First, they installed a zinc-reacting protecting ring, which changed its physical properties and made it easier to target. They also attached an "address tag" to the ZP1, directing it to the mitochondria. This tag, a derivative of triphenylphosphonium, is both positively charged and hydrophobic. The resulting sensor easily entered the cells, which allowed them to visualize pools of mobile zinc within the mitochondria.

Inside the mitochondria of epithelial prostate cells, zinc is known to inhibit the metabolic enzyme, aconitase. The scientists believe that by blocking aconitase, zinc shortens the citric acid cycle, which are the series of reactions needed to produce adenosine triphosphate (ATP). Most ATP production occurs in the mitochondria, and the MIT team theorized that when prostate cells become cancerous, they banish zinc from there, allowing the cancer cells to produce the extra energy they need to grow and divide. The scientists found that although the cancerous prostate cells absorbed the zinc, it did not collect in the mitochondria.

Robert Radford, PhD, the senior author of the paper said, “We can use these tools to study zinc trafficking within prostate cells, both healthy and diseased. By doing so, we're trying to gain insight into how zinc levels within the cell change during the progression of prostate cancer.” The study was published on December 12, 2013, in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Related Links:
Massachusetts Institute of Technology
Photon Technology International
Bruker Daltonics