Published September 11, 2014
Wilma A. Hofmann, PhD, assistant professor of physiology and biophysics, will study cellular processes that cause high levels of unsaturated fats to increase the metastatic potential of prostate cancer cells.
The study will shed new light on why overweight men face a far greater risk of developing aggressive prostate cancer than men of healthy weight.
Results may lead to novel therapeutic approaches for managing cancer metastasis as well as new diagnostic biomarkers that could help detect aggressive prostate cancer earlier and prevent its progression.
To conduct the three-year study, Hofmann received a $598,000 Idea Development Award from the U.S. Department of Defense Congressionally Directed Medical Research Programs.
Through previous studies, Hofmann and her colleagues found that the cellular uptake of certain types of excess fats causes enhanced secretion of components required for cells to metastasize, or leave the site of a primary tumor and invade surrounding tissues.
Thus, the presence of excess fats can be causally linked to an increase in the metastatic potential of prostate cancer cells.
Hofmann says she expects results of the new study to fundamentally enhance our understanding of the cause of cancer progression through the discovery of mechanisms that lead to metastatic behavior of cancer cells.
The new research will test whether micro-environmental fats alter the membrane composition of fluid-filled vesicles destined for secretion. The vesicle membrane, like the plasma membrane — the cell’s barrier — is comprised of layers of lipid molecules or fatty acids.
These alterations, researchers hypothesize, may increase secretion efficiency.
The research team aims to identify cellular and molecular components and pathways that facilitate enhanced secretion of vesicles with altered lipid content.
“We will establish the mechanisms by which fatty acids contribute to metastatic phenotypes by analyzing the biological consequences of altered fat levels on secretion, motility and invasiveness of human prostate cancer cells,” Hofmann says.
“This knowledge is highly likely to provide new targets that can be manipulated pharmacologically, resulting in new and innovative approaches for treatment of cancer progression.”
Hofmann’s team also seeks to identify noninvasive biomarkers for two key purposes: to distinguish aggressive cancer from indolent or clinically insignificant disease and to assess the prognosis of aggressive prostate cancer, aiding early detection.
The researchers hypothesize that disease outcome and progression quantitatively correlate with the lipid composition of secreted vesicles and, therefore, analyzing this composition can be used to grade the metastatic potential of cancer cells.
“Currently, no such marker is available, making correct diagnosis and treatment of aggressive prostate cancer difficult,” Hofmann notes.
“If successful, our results could greatly improve diagnostics and treatment and will directly contribute to helping patients and clinicians decide on treatment options.”
Patients with clinically insignificant cancer may be able to avoid unnecessary treatment, such as radiation or biopsies, for example.
Conversely, patients with clinically significant cancer could choose early, rigorous treatment, leading to more favorable clinical outcomes.
Prostate cancer is the most common cancer in men and the second-leading cause of cancer deaths nationwide. Most deaths from prostate cancer are caused by metastasis.
“Considering that the number of obese or overweight adults is on the rise, it is urgent to understand the cellular processes that facilitate the development of metastatic prostate cancer,” Hofmann says.