Periprostatic Adipose Tissue: A New Perspective for Diagnosing and Treating Prostate Cancer

Abstract

Prostate cancer (PCa) is the most common tumor of the male genitourinary system. It will eventually progress to fatal metastatic castration-resistant prostate cancer, for which treatment options are limited. Adipose tissues are distributed in various parts of the body. They have different morphological structures and functional characteristics and are associated with the development of various tumors. Periprostatic adipose tissue (PPAT) is the closest white visceral adipose tissue to the prostate and is part of the PCa tumor microenvironment. Studies have shown that PPAT is involved in PCa development, progression, invasion, and metastasis through the secretion of multiple active molecules. Factors such as obesity, diet, exercise, and organochlorine pesticides can affect the development of PCa indirectly or directly through PPAT. Based on the mechanism of PPAT's involvement in regulating PCa, this review summarized various diagnostic and therapeutic approaches for PCa with potential applications to assess the progression of patients' disease and improve clinical outcomes.

Keywords: and treatment; diagnosis; inflammation; lipids; periprostatic adipose tissue; prostate cancer.

Figure 1

Influence of periprostatic adipose tissue on prostate cancer. Periprostatic adipose tissue (PPAT) consists of many adipocytes, other non-adipocytes, connective tissue matrix, blood vessels, and nerve tissues. The non-adipocyte components include inflammatory cells (macrophages), immune cells, preadipocytes, and fibroblasts. These components, as a whole, are capable of secreting various factors that influence the biological behavior of PCa in a paracrine or endocrine manner, including metabolic reprogramming, proliferation, and epithelial-to-mesenchymal transition (EMT) invasion. Some of these factors promote PCa progression, such as IL-6, leptin, VEGF, and CCL7; however, there are protective factors, such as adiponectin, and the effect on PCa depends on the balance between these two kinds of factors. In turn, PCa regulates the biological behavior of adipose tissues, thus promoting its development. Obesity and diet may enhance the effect of PPAT in an endocrine manner. Diet and exercise may indirectly alter PPAT function by affecting obesity or directly change the function of PPAT, and organochlorine pesticide deposition in PPAT may also affect PPAT function. Abbreviations CLS: crown-like structure; PCa: prostate cancer; IL-6: interleukin 6; MMPs: matrix metalloproteinases; TGF-β: transform growth factor-β; VEGF: vascular endothelial growth factor; IGF-1: insulin-like growth factor; CCL7: C-C motif ligand chemokine 7; CXCL 12: C-X-C motif ligand chemokine 12; MCP-1: monocyte chemoattractant protein 1.

Figure 2

PPAT has potentially valuable clinical applications. The clinical applications of PPAT can be divided into diagnostic and therapeutic approaches. Diagnostic approaches focus on applying PPAT imaging parameters, genomics, and lipidomics. Therapeutic approaches can be in molecularly targeted drugs, lifestyle interventions, and surgical approaches to decision-making. Imaging parameters can be used to assess the aggressiveness of PCa, time to CRPC, and patient prognosis. PPAT lipid metabolism genomic and epigenetic assays can be used to predict high-risk PCa. Lipidomic assays can be used to assess the PCa lipid metabolism microenvironment and predict high-risk PCa. Life style intervations and targeted drugs can improve the effect of treatment. The amount and distribution of PPAT can serve as a consideration for the surgeon to predict the surgical plan. Abbreviations: PPAT: periprostatic adipose tissue; PPFT: periprostatic fat thickness; PPFA: periprostatic fat area; PPFD: periprostatic fat density; PPFR: periprostatic fat ratio; PCa: prostate cancer.