Advancing prostate cancer research: an exploration of periprostatic adipose stem cells

Abstract

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.

Keywords: Adipose stem cells; Benign prostatic hyperplasia; Endocrine disruptors; Exosomes; Gene therapy; Periprostatic adipose tissue; Prostate cancer; Therapeutic carriers.

Fig. 1

Venn diagram illustrating the overlap of proteins identified in Vesiclepedia derived from exosomal vesicles of mesenchymal stem cells, compared with proteins of conditioned media of periprostatic adipose tissue in patients with stage, stage T2 prostate cancer and Benign Prostatic Hyperplasia (a). Bar chart depicting biological pathways associated with exosomal proteins from conditioned media of periprostatic adipose tissue in patients with stage T3 prostate cancer (b)