Sticky Treatment With E-cadherin May Stop Prostate Cancer Metastasis

August 2, 1999. -- University of Iowa Health Care researchers may have found a way to help prevent prostate cancer from spreading, according to research findings in the Aug. 1 issue of the journal Cancer Research. The work is still in an early stage but it fits with a quite well-developed line of research.

E-cadherin is a cell adhesion gene. In the prostate it acts a suppressor of cells that try to metastasize. Using calcium, it helps keep cells normally differentiated and "glued" to each other. For about ten years it has been investigated as a possible "invasion suppressor." E-cadherin is one of a group of genes that may be inactivated or downregulated during progression to advanced prostate cancer The UI team have found a way to restore E-cadherin so as to hinder the ability of prostate cancer to spread.

Mary J.C. Hendrix, Ph.D., professor and head of anatomy and cell biology; did this work with her graduate student, Jun Luo; and collaborator David M. Lubaroff, Ph.D., UI professor of urology,

"The results of this study provide a potential new therapeutic strategy for targeting invasive prostate cancer," said Hendrix. "The correlation between the expression of the E-cadherin protein and the spreading of prostate cancer to distant sites may provide another weapon in the battle against this deadly disease," added Lubaroff, the associate director for research infrastructure for the UI Cancer Center.

Prostate cancer is the most commonly diagnosed cancer and is the second leading cause of cancer death in American men. Although today the disease can be diagnosed and treated at early stages, almost 40,000 men a year die from prostate cancer that has spread. to their bones or to lungs, liver or other organs.

"The progression of the disease involves a number of steps, including discrete molecular changes," Hendrix explained. "It is crucial to identify the molecular changes and understand how they fit into the disease progression in order to develop better therapeutic approaches to manage prostate cancer."

Hendrix and her colleagues knew from previous studies that disruptions in the E-cadherin complex happen in many advanced forms of cancer. E-cadherin, named for adhering or gluing, helps to maintain the integrity of normal epithelial cells.

With data from laboratory experiments and clinical biopsies, UI researchers and other investigators elsewhere had suggested there was a correlation between the decreased E-cadherin and the ability of prostate cancer to spread. However, until this most recent UI study, there was no direct evidence to support the idea that genetic reintroduction of E-cadherin could suppress prostate cancer invasion.

Using prostate cancer cells from a rat model, the UI investigators restored missing or deficient E-cadherin in the cells. The results showed that the strategy drastically enhanced the ability of the prostate cancer cells to adhere to each other, thus restoring their epithelial integrity and making them more normal. The approach also suppressed the release of enzymes known to take part in cancer invasion through organs and tissues in the body.

The UI team is now involved in gene therapy studies to put E-cadherin back into prostate cancer cells so as to put a brake on the ability of these cells to invade and spread.

"The outcome of these studies could form the basis of the development of new clinical strategies for the treatment of prostate cancer,"" Hendrix said.

Richard D. Williams, M.D., UI professor and head of urology added: "This study is a prime example of the enormous potential that molecular biologic techniques have to change the behavior of cancer cells." If it can be applied to patients, he said, this discovery may limit the spread of prostate cancer within the body and thus improve survival.

Meanwhile, researchers in breast cancer and other cancers have been testing retinoids and specific types of vitamin D to see if they restore E-cadherin. UCLA researchers have done a promising study on the effects of this combination on prostate cancer cells.

Dr. Mary J. Hendrix is the associate director of basic research and deputy director for the UI Cancer Center at University of Iowa
Cancer Res 1999;59:3552-3556.

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Aug 2 1999

"Sticky" Protein, E-Cadherin, May Prevent Prostate Cancer from Spreading