City of Hope researchers have developed a tiny synthetic homing device that could improve prostate cancer diagnosis.
The scientists reported their latest results on this nanotechnology in the June issue of the journal Nanomedicine published by London’s Future Medicine.
The team comprised the Division of Urology and Urologic Oncology’s Steve Smith, Ph.D., professor, Elizabeth Singer, Ph.D., staff scientist in Smith’s laboratory, Laura Crocitto, M.D., associate professor, and Timothy Wilson, M.D., Pauline and Martin Collins Family Chair in Urology; Sofia Loera, senior research associate in the Department of Pathology; Yuri Choi and Lawrence Weiss, M.D., both formerly of City of Hope; and S. Ashraf Imam, Ph.D., of Huntington Medical Research Institute.
Nanotechnology attempts to build materials or tools on a nanometer scale: constructs so tiny that tens of thousands of them would fit within the width of a human hair.
|A 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)|
Their device is a Y-shaped DNA molecule containing a fluorescent dye called fluorescein that glows under blue light. The scientists link a protein to each of the arms of the Y. These linked proteins include ligands that target the device to other proteins that are found in the body — like the enzymes called thioredoxin reductases, which are involved in the body’s defenses against oxidative damage. Thioredoxin reductases are active in some cancers.
In the current study, the scientists used frozen prostate tissue samples taken from men with prostate cancer and exposed them to a solution containing their nanodevice. They then shined blue light on the samples, and as they hoped, the tumor tissue glowed.
|Elizabeth Singer, right, and Steve Smith are seeking better ways to diagnose prostate cancer. (Photo by Darrin S. Joy)|
To their surprise, however, the area surrounding the tumor itself (called the stromal region or the tumor microenvironment) was much brighter than tumor tissue. Stromal tissue normally surrounds the secretory cells in the prostate gland. When a cancer forms, the stromal cells in the microenvironment around the tumor react as though the gland had been wounded: They turn into what is called reactive stroma, much like the stromal cells in the skin respond to a cut.
“We found that this reactive tumor stroma appears to overproduce two forms of thioredoxin reductase,” Singer said.
The results suggest that the stroma near the growing tumor is intimately connected to the development of the tumor. This could lead to more accurate diagnosis of the disease, according to the researchers.
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.
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 results also might give scientists a better understanding of how prostate cancer escapes the body’s defenses, according to Smith. “Ordinarily the stromal wound response is designed to fight bacteria that might enter a wound. So the reactive stroma secretes lethal chemicals like bromine and hydrogen peroxide into the wound. Apparently, the stroma produces the thioredoxin reductases to protect itself from those compounds.
“This is an evolutionary response that has been selected for its ability to kill bacteria, but it actually makes the cancer evolve faster,” he said.
Singer said the findings also 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,”she said.
These results add to growing evidence that stroma may be key to many cancers’ development.
Future studies in the laboratory are aimed at altering the nanodevice so that it can deliver therapeutics to the stroma.
The National Cancer Institute and the Congressionally Directed Medical Research Program of the U.S. Army funded the study.