Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia

Abstract

Background/Aim: Periprostatic adipose tissue (PPAT) directs tumour behaviour. Microenvironment secretome provides information related to its biology. This study was performed to identify secreted proteins by PPAT, from both prostate cancer and benign prostate hyperplasia (BPH) patients. Patients and Methods: Liquid chromatography-mass spectrometry-based proteomic analysis was performed in PPAT-conditioned media (CM) from patients with prostate cancer (CMs-T) (stage T3: CM-T3, stage T2: CM-T2) or benign disease (CM-BPH). Results: The highest number and diversity of proteins was identified in CM-T3. Locomotion was the biological process mainly associated to CMs-T and reproduction to CM-T3. Immune responses were enriched in CMs-T. Extracellular matrix and structural proteins were associated to CMs-T. CM-T3 was enriched in proteins with catalytic activity and CM-T2 in proteins with defense/immunity activity. Metabolism and energy pathways were enriched in CM-T3 and those with immune system functions in CMs-T. Transport proteins were enriched in CM-T2 and CM-BPH. Conclusion: Proteins and pathways reported in this study could be useful to distinguish stages of disease and may become targets for novel therapies.

EGCG Inhibits Adipose-Derived Mesenchymal Stem Cells Differentiation into Adipocytes and Prevents a STAT3-Mediated Paracrine Oncogenic Control of Triple-Negative Breast Cancer Cell Invasive Phenotype

“…Adipogenesis, as defined by the formation of adipocytes from stem cells [ 1 ], and the adipose tissue itself have drawn much attention at the onset of chronic inflammation in metabolic diseases, such as type 2 diabetes mellitus, cardiovascular diseases, and in several types of cancer [ 2 , 3 ]. Among the processes involved in the setting of these diseases, the adipose tissue secretome has been inferred to play a crucial paracrine regulatory role in brain cancer [ 4 ], prostate cancer [ 5 ], bladder cancer [ 6 ], breast cancer [ 7 ], and colon cancer [ 8 ]. Molecular links between central obesity and breast cancer have also been inferred to trigger oncogenic signaling pathways, including NFκB, JAK, STAT3, and AKT [ 9 ].…”

Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue

“…Pertinent to the endocrine nature of the AT, PPAT adipocytes and stromovascular cells secrete a myriad of adipokines capable of modulating PCa behavior, probably under the instruction of PCa cells [ 147 , 148 , 149 ]. Indeed, profound alterations in the PPAT epigenome, transcriptome, and secretome have been shown in lean and obese patients with benign prostatic hypertrophy (BPH), non-aggressive, and aggressive PCa [ 150 , 151 , 152 , 153 ]. Importantly, proliferative and metabolic pathways were differentially regulated according to the stage of disease [ 150 , 151 ].…”

Tumor Microenvironment in Prostate Cancer: Toward Identification of Novel Molecular Biomarkers for Diagnosis, Prognosis, and Therapy Development

“…Also, Ribeiro et al (2012) revealed that PPAT produces MMPs that degrade the prostatic ECM facilitating tumoral dissemination and progression into metastatic PCa. Therefore, targeting signaling pathways and secreted factors within the PPAT could be useful in limiting PCa advancement ( Sacca et al, 2019 ).…”