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.

Keywords: Periprostatic adipose tissue; benign prostate hyperplasia; fat tissue; microenvironment; prostate cancer; proteomic; secretome.

Figure 1. Distribution of proteins detected in conditioned media of periprostatic adipose tissue according to their molecular weights (MW) as obtained from MS analysis (A). Venn diagram depicting the number of specific and common proteins (B).

Figure 2. Protein categorization using the PANTHER classification system and annotated with ontology terms (GO). (A) Molecular functions, (B) Biological processes, (C) Cellular components, (D) Protein classes.

Figure 3. Column charts of the subcellular localization of proteins. A) CM-T3. B) CM-T2. C) CM-BPH. Bar chart of represented cellular compartments (D); molecular functions (E) and biological processes (F), according to FunRich analysis.

Figure 4. Bar charts of enrichment and depletion of molecular functions in the secretome of CM-T3 compared to CM-BPH (A); CM-T2 compared to CM-BPH (B) and CM-T3 compared to CMT2 (C). Enrichment and depletion of biological processes in the secretome of CM-T3 compared to CM-BPH (D), CM-T2 compared to CM-BPH (E) and CM-T3 compared to CM-T2 (F), according to FunRich analysis.

Figure 5. Bar charts of exclusive enriched biological pathways for CMs-T (A) and for CM-T3 (B). Bar charts of sites of protein expression (C and D). Bar charts of relative exponentially modified protein abundance index (emPAI) with at least two-fold change. (E) Between CM-T3, CM-T2 and CM-BPH; (F) between CM-T2 and CM-T3; (G) between CM-T3 and CM-BPH, according FunRich analysis.