Exosomes Derived from Irradiated-Prostate Cancer Cells Promote Cancer Progression

Radiotherapy (RT) is a commonly employed therapeutic strategy for the treatment of localized cancers, including prostate cancer (PCa). Despite significant advancements in radiotherapy technology over recent years, high recurrence and metastasis of PCa after RT remain critical challenges. Various mechanisms have been implicated in how cancer evades radiotherapy, and exosomes, a type of extracellular vesicles (EVs) has recently been identified as one of the contributing factors. This study aimed to investigate whether exosomes derived from irradiated PCa cells are involved in the cancer progression and to identify possible key factor in this process.

Exosomes were isolated from irradiated or non-irradiated PCa cell lines (designated as Rad-Exo or Exo) and characterized by specific marker expression, morphology and size. PCa cells treated with Rad-Exo or Exo were analyzed for the effects of proliferation, specific gene expression, migration and cancer stem cell property. Differential protein expression in Rad-Exo and Exo were carried out by mass spectrometry.

Results showed that, compared to Exo, Rad-Exo treatment inhibited cell proliferation but significantly promoted migration and elevated the expression of genes related to epithelial to mesenchymal transition. Additionally, cells treated with Rad-Exo showed increased expression of genes related to cancer stem cells. Mass spectrometry identified POTEE as more abundant within Rad-Exo then in Exo, and its expression was confirmed to be elevated in PCa cells following irradiation. Furthermore, POTEE expression increased in cells after Rad-Exo treatment.

This study suggests that exosomes derived from irradiated PCa cells may function as a driver of cancer progression, including recurrent or metastatic cancer. Also, exosomal POTEE may serve as a potential target for future therapeutic or diagnostic investigations in prostate cancer.