Development of an Ex Vivo Bioassay to Examine Modulation of PSA-Positive Macrophage Invasiveness and Inflammatory Activities in Prostate Cancer Patients with Abdominal Obesity—The Identification of New Biomarkers May Be Able to Assess the Effectiveness of Diet and Lifestyle Changes

Investigator: David Heber, MD, PhD–Professor, Medicine and Public Health, Director, Center for Human Health, Chief, Division of Clinical Nutrition in the Department of Medicine, University of California, Los Angeles

Macrophages are specialized white blood cells that scavenge invading microbes and dead cellular material. They are also involved in inflammation, angiogenesis, and metastasis. Accumulated abdominal fat and metabolic syndrome, two common findings in prostate cancer patients, activates macrophages. However, this activity is reversible with diet and lifestyle changes. This creative project proposes to study prostate cancer-associated macrophages both in the lab and in patients. These cancer-associated macrophages will be tested as a progression biomarker for successful alterations in lifestyle and might represent a meaningful endpoint for pharmacological intervention between obesity and inflammation.

Progress Report:

Epidemiological studies have revealed that obese men with prostate cancer have poor prognosis and an elevated risk of prostate cancer specific death. Increased inflammation caused by activated macrophages (specialized white blood cells) in obese men may be a significant contributing factor, as these cells have been shown to be involved in prostate cancer progression and metastasis. Dr. Heber is studying the molecular differences between activated macrophages isolated from the blood of lean men and obese men. His research team has designed an ex vivo (outside of the body) assay using prostate cancer cells grown in suspension as spheroids (balls of cells). These prostate cancer spheroids are then exposed to activated macrophages from either lean or obese men. Early data shows that activated macrophages from obese men readily invade the prostate cancer spheroids unlike macrophages from lean men. Future investigations will determine how the interaction between the activated macrophages from obese men and prostate cancer cells stimulates cancer cell growth and survival. Ultimately, the hope is to use this assay as a rapid test for potentially useful nutritional and pharmacological interventions in advanced prostate cancer, whereby active agents would result in a reduction in activated macrophage invasion of the prostate cancer spheroids.