Adipose microenvironment is involved in signaling pathways that influence breast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumor human breast epithelial cell lines when incubated with conditioned media (CMs) from human breast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants (hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. non tumor associated adipocytes. We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines. We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell lines or in the different CMs. In addition we evaluated changes in the morphology and expression of these factors in slices of the different adipose tissues. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey’s post-hoc tests were performed within each individual treatment. hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breast cancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expression compared to hATN-CMs. In addition, we observed a loss of effect in cellular migration when we pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains bound to the versican core protein, thus losing the ability to bind to CD44. Adipocytes associated with the invasive front are reduced in size compared to adipocytes that are farther away. Also, hATT adipocytes express significantly higher amounts of versican, CD44 and Adipo R1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes. We conclude that hATT secrete a different set of proteins compared to hATN. Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared to hATN-CMs, might be involved in the tumorogenic behavior observed in both cell lines employed. In addition, we may conclude that adipocytes from the tumor microenvironment show a less differentiated state than adipocytes from normal microenvironment. This would indicate a loss of normal functions in mature adipocytes (such as energy storage), in support of others that might favor tumor growth.

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.

The periprostatic adipose tissue (PPAT) is a site of invasion of prostate cancer (PCa) and is part of the microenvironment. It was shown that PPAT secretes factors and fatty acids (FAs) that alter the microenvironment of the PCa. The PPAT secretome of patients with PCa-T3 stage (PPAT-T3) has a metabolic profile enriched in several pathways related to energy production, indicating a greater energy requirement by the tumor, when compared to that of patients in the PCa-T2 stage (PPAT-T2). PPAT-T3 also shows enrichment in pathways related to hormone response, polyamine synthesis, and control of protein synthesis, through amino acid, RNA, and nucleotide metabolism. PPAT-T2 and PPAT-BPH secretomes have less complex metabolic profile, both related with energy balance, while PPAT-BPH has hormone response through insulin pathway. Undoubtedly, a deeper characterization of the human PPAT will lead to a better understanding of the disease and possibly allow new stratification factors and the design of a specific therapy that targets crucial components of the tumor microenvironment as another way to treat or control the disease.

Prostate cancer (PCa) is the most prevalent cancer among men, highlighting the urgent need for innovative treatment strategies. The periprostatic adipose tissue (PPAT) plays a crucial role in the PCa tumor microenvironment, with direct crosstalk between PPAT and PCa cells, particularly in advanced stages with extraprostatic extension—a feature linked to poor prognosis. Owing to their migratory capacity, adipose stem cells (ASCs) are promising in regenerative medicine and play a key role in tissue engineering and cancer research. These findings offer potential for novel approaches in targeted drug delivery and gene therapy for PCa. While ASCs within PPAT influence the tumor stroma, the mechanisms behind their interactions with PCa cells are not fully understood, with studies reporting both inhibitory and promoting effects on cancer progression. The adipose tissue secretome, including PPAT-ASC exosomal proteins, mediates communication between PPAT and PCa cells, with exosomal dysregulation observed in stage T3 PCa. This dysregulation implicates key cancer pathways such as integrin-mediated cell interactions, epithelialmesenchymal transition, and mRNA stability regulation. Although ASCs show promise as therapeutic carriers, their use is complicated by the need to prevent unwanted interactions with cancer cells. Moreover, environmental contaminants such as endocrine disruptors can alter ASC behavior, potentially influencing PCa development. This review synthesizes current knowledge on the multifaceted roles of ASCs and ASC-derived exosomes in PCa biology, their therapeutic applications, and the impact of environmental toxicants on their function and cancer-related outcomes. Further research into the underlying biological mechanisms is needed, highlighting the need for safe, targeted therapeutic approaches in PCa treatment.