4.2 Article

Impact of umbilical cord mesenchymal stromal/stem cell secretome and cord blood serum in prostate cancer progression

Journal

HUMAN CELL
Volume 36, Issue 3, Pages 1160-1172

Publisher

SPRINGER JAPAN KK
DOI: 10.1007/s13577-023-00880-z

Keywords

Umbilical cord; Mesenchymal stem; stromal cells; Prostate cancer; Cord blood serum; Acellular therapy

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Prostate cancer is the second most common malignancy in men and has a high mortality rate. This study found that umbilical cord-derived mesenchymal stem cells (UC-MSC) and cord blood serum (CBS) contain various growth and anti-inflammatory factors that can regulate tumor cell proliferation, survival, and immune response. When exposed to UC-MSC-conditioned medium or CBS, prostate cancer cells showed reduced viability, proliferation, and motility, while non-malignant prostate cells were unaffected. Additionally, UC-MSC and CBS altered the expression of genes related to the AKT/PI3K pathway, p53, and interleukins, leading to a more anti-inflammatory expression profile in the malignant prostate cancer cells.
Prostate cancer (PCa) is the second most common malignancy in men, and the fifth leading cause of death worldwide. Mesenchymal stromal/stem cells (MSC) have been identified in PCa, although contradictory effects in malignant transformation and tumor progression have been described. Since umbilical cord (UC) MSC and cord blood serum (CBS) are rich in numerous growth and anti-inflammatory factors, UC-MSC secretome and CBS are able to modulate tumor cell proliferation and survival as well as immunity and angiogenesis. In the present study, we address this relationship and investigate the influence of UC-MSC secretome and CBS on two human PCa cell lines (PC3 and LNCaP) and a normal epithelial prostate cell line (HPEpiC). Our results disclosed that upon exposure to UC-MSC-conditioned medium or CBS, both PC3 and LNCaP cells exhibited reduced viability, proliferation, and motility while non-malignant epithelial prostate cells were unaffected. These findings were corroborated by expression analysis of AKT/PI3K signaling pathway, p53 and interleukin genes. UC-MSC and CBS factors decreased the expression of growth-stimulating AKT and PI3K effectors and simultaneously up-regulated the expression of tumor-suppressor p53. Moreover, a more anti-inflammatory expression profile was found in both malignant PCa cell lines. Altogether, these results shed light into possible mechanisms by which UC-MSC and CBS reduce PCa progression, further reinforcing their potential use as novel therapeutic agents in PCa. [GRAPHICS] .

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