Interplay between Prostate Cancer and Adipose Microenvironment: A Complex and Flexible Scenario

Abstract

Adipose tissue is part of the prostate cancer (PCa) microenvironment not only in the periprostatic area, but also in the most frequent metastatic sites, such as bone marrow and pelvic lymph nodes. The involvement of periprostatic adipose tissue (PPAT) in the aggressiveness of PCa is strongly suggested by numerous studies. Many molecules play a role in the reciprocal interaction between adipocytes and PCa cells, including adipokines, hormones, lipids, and also lipophilic pollutants stored in adipocytes. The crosstalk has consequences not only on cancer cell growth and metastatic potential, but also on adipocytes. Although most of the molecules released by PPAT are likely to promote tumor growth and the migration of cancer cells, others, such as the adipokine adiponectin and the n-6 or n-3 polyunsaturated fatty acids (PUFAs), have been shown to have anti-tumor properties. The effects of PPAT on PCa cells might therefore depend on the balance between the pro- and anti-tumor components of PPAT. In addition, genetic and environmental factors involved in the risk and/or aggressiveness of PCa, including obesity and diet, are able to modulate the interactions between PPAT and cancer cells and their consequences on the growth and the metastatic potential of PCa.

Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis

“…The periprostatic space, which is surrounded by adipocytes, may perform an endocrine function in malignant tumor behavior. Cancer cells can cause adipocytes to become smaller, disperse lipid droplets, and acquire a fibrous phenotype, forming tumor-associated adipocytes; additionally, these adipocytes secrete large amounts of cytokines and provide energy for tumor proliferation and metastasis and thus increase tumor malignant potential ( 26 , 27 ). Therefore, we focused on the relationship between MMP-12 in cancer cells and adipocytes.…”

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

“…PPAT is an active secretory organ that can affect the PCa lipid microenvironment and inflammatory state, thus promoting PCa progression by secreting lipids, adipokines, and hormones in a paracrine or endocrine manner. PPAT also directly contacts PCa or mediate communication between PPAT and PCa in an exocytic manner 26 , 27 . In turn, PCa regulates the biological behavior of adipose tissues, thus promoting its development 26 , 28 , 29 .…”

Variable effects of periprostatic adipose tissue on prostate cancer cells: Role of adipose tissue lipid composition and cancer cells related factors

“…PPAT stores energy reserves in the form of triglycerides and is also a metabolically dynamic active organ. Previous studies have suggested an important role for PPAT in the modulation of PCa progression and aggressiveness, through adipokine or fatty acid (FA) release 6,7 . Although most of the mediators released by PPAT are likely to promote tumor progression, others, such as some polyunsaturated FAs (PUFAs) and adiponectin, have been shown to have antitumor properties 6 .…”

“…Previous studies have suggested an important role for PPAT in the modulation of PCa progression and aggressiveness, through adipokine or fatty acid (FA) release 6,7 . Although most of the mediators released by PPAT are likely to promote tumor progression, others, such as some polyunsaturated FAs (PUFAs) and adiponectin, have been shown to have antitumor properties 6 . A specific FA profile of PPAT has previously been associated with features of PCa aggressiveness, characterized by low levels of eicosapentaenoic acid (EPA, an n‐3 PUFA) 8 .…”

“…6,7 Although most of the mediators released by PPAT are likely to promote tumor progression, others, such as some polyunsaturated FAs (PUFAs) and adiponectin, have been shown to have antitumor properties. 6 A specific FA profile of PPAT has previously been associated with features of PCa aggressiveness, characterized by low levels of eicosapentaenoic acid (EPA, an n-3 PUFA). 8 The heterogeneity of the interplay between PPAT and PCa cells is also suggested by in vitro studies showing that the effects of lipids on PCa cell migration differ according to the type of FA.…”