Periprostatic adipose inflammation: A targetable mediator of prostate cancer progression

About Periprostatic adipose inflammation: A targetable mediator of prostate cancer progression
  • Obesity is a risk factor for the development and progression of prostate cancer and obese patients develop more aggressive disease with poorer survival. The role of obesity in promoting cancer is largely through aberrant interactions with the immune system. Interactions with adipose (fat) cells cause immune cells to become chronically activated and produce molecules that promote tumor progression and growth. Understanding the biology by which obesity and chronic inflammation cooperate to promote prostate cancer will lead to new treatment strategies for patients.
  • Dr. Andrew Dannenberg and team have observed that prostate cancer patients have inflammation in the fat tissue surrounding their prostates. They have observed a phenomenon termed “crown-like structures” (CLS) in which phagocytic immune cells surround dying fat cells and produce tumor-promoting molecules. CLS are linked to more aggressive disease in breast cancer patients. Using tissues from men who have undergone radical prostatectomies, whether CLS are linked to tumor aggressiveness and chronic inflammation in prostate cancer patients will be determined. Metabolites from blood samples from patients will be profiled to generate a prognostic tool that indicates the presence of CLS in prostate fat tissues.
  • Whether a patient’s body mass index (BMI), level of exercise, and medication use associate with the presence of CLS will be determined. Finally, a clinical trial testing the impact of aerobic exercise on the presence of CLS in prostate cancer patients will be conducted.
  • These studies will determine whether CLS are a mechanism by which obesity and chronic inflammation cooperate to promote prostate cancer, and lead to new treatment strategies for obese prostate cancer patients.

What this means for patients: Obesity is a major cause of chronic inflammation which promotes the development and progression of malignancies. This project will explore the role of a distinct fat cell-immune cell interaction in prostate cancer progression, develop prognostic tools that predict these interactions, and explore the effect of exercise and lifestyle activities on this phenomenon. These discoveries will contribute to the knowledge of how obesity and inflammation promote prostate cancer, and lead to treatment strategies and lifestyle changes that prevent prostate cancer progression.

Principal Investigator:

Andrew Dannenberg, MD (Weill Cornell Medical College)

Co-investigators:

Kotha Subbaramaiah, PhD (Weill Cornell Medical College), Xi Kathy Zhou, PhD (Weill Cornell Medical College), Howard Scher, MD (Memorial Sloan Kettering Cancer Center), Peter Scardino, MD (Memorial Sloan Kettering Cancer Center), James Eastham, MD (Memorial Sloan Kettering Cancer Center), Clifford Hudis, MD (Memorial Sloan Kettering Cancer Center), Lee Jones, PhD (Memorial Sloan Kettering Cancer Center), Ayca Gucalp, MD (Memorial Sloan Kettering Cancer Center), Neil Iyengar, MD (Memorial Sloan Kettering Cancer Center), Dilip Giri, MD (Memorial Sloan Kettering Cancer Center).