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Prostate cancer’s mighty tiny foe 

 


By Darrin S. Joy


They may be incredibly tiny, but nanotechnology devices, or nanodevices, are set to make a huge impact on medicine. And City of Hope researchers are leaders in the field.

Nanotechnology attempts to build materials or tools on a nanometer scale: devices so tiny that tens of thousands of them would fit within the width of a human hair.

Scientists from the Division of Urology and Urologic Oncology and the Department of Pathology are working on a tiny synthetic homing device that could improve prostate cancer diagnosis and treatment.

The City of Hope team’s device is a Y-shaped DNA molecule containing a fluorescent dye that glows when blue light is shined on it.

On each arm of the “Y” the scientists linked a special protein molecule that targets the device to key enzymes in the body. Many cancers overproduce these enzymes, which are called thioredoxin reductases.

Diagram of Y-shaped DNA molecule nanodeviceA tiny nanodevice consists of a Y-shaped DNA molecule (blue) linked to three targeting molecules (red, yellow and purple) and a fluorescent dye (green). The device binds to tissue surrounding prostate tumors and glows green under blue light (inset). (Image courtesy of the Urology Nanolab)
In the current study, the researchers used frozen prostate tissue samples taken from men with prostate cancer and exposed them to a solution containing the nanodevice. They then shined blue light on the samples. As they hoped, the tumor tissue glowed.

But to their surprise, the area surrounding the tumor — called the stromal region — glowed even brighter than the tumor tissue itself.

Stromal tissue normally surrounds and supports a gland or organ. When a prostate tumor forms, the stromal cells in the nearby area react as though the gland has been wounded, much like the stromal cells in the skin respond to a cut: They turn into what’s called reactive stroma.

“We found that this reactive tumor stroma appears to overproduce two forms of thioredoxin reductase,” said Beth Singer, Ph.D., urology and urologic oncology staff scientist.

The finding suggests that the stroma near the growing tumor is closely connected to the development of the tumor. And this could lead to more accurate diagnosis of the disease, according to the researchers.

Here’s why that’s important.

Clinicians currently screen for prostate cancer by checking prostate specific antigen, or PSA, levels in the blood. If levels are abnormal, the clinician will check for cancer with an expensive and sometimes painful biopsy procedure. If the biopsy shows no cancer but PSA levels remain high over time, the physician will repeat the biopsy at further expense and more patient discomfort, just to be sure there’s really no cancer.

But using the nanodevice to test the stroma in the biopsy sample could make the first biopsy all that is necessary.

“If we see the stroma light up, it probably means cancer is present,” Singer said, though she cautioned that more research is necessary to confirm the connection.

The study also might provide a better understanding of how prostate cancer escapes the body’s defenses, according to Steven Smith, Ph.D., professor of urology and urologic oncology.

The stromal response is designed to fight bacteria that might enter a wound by generating harmful chemicals, and the reactive stroma produces thioredoxin reductases to protect itself from those very same chemicals.

“This is an evolutionary response that has been selected for its ability to kill bacteria, but it actually makes the cancer evolve faster,” Smith said.

Singer said the findings have implications for treatment. “It makes the stroma an attractive target for therapeutics, because attacking the stroma instead of the tumor could counteract its ability to promote tumor growth.”

City of Hope recently posted helpful videos explaining why men should care about prostate cancer and why screening is important on its YouTube channel. Visit www.youtube.com/cityofhopeonline to view those and other City of Hope videos.

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