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

Autores da FMUP

• Alexandra Isabel Coelho De Sousa

  Autor

• Raquel Ângela Silva Soares Lino

  Autor

Participantes de fora da FMUP

• Coelho, P
• Leite, F
• Teixeira, C
• Rocha, AC
• Santos, I
• Baylina, P
• Fernandes, R
• Costa, R
• Gomes, A

Unidades de investigação

• Biomedicina

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• Medicina

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

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] .

Keywords

• Humans; Male; Phosphatidylinositol 3-Kinases; Prostate; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Secretome; Serum; Stem Cells; Tumor Suppressor Protein p53; Umbilical Cord; protein p53; phosphatidylinositol 3 kinase; protein kinase B; protein p53; angiogenesis; Article; cancer growth; cell culture; cell proliferation; cell viability; controlled study; Cytomegalovirus; cytotoxicity; cytotoxicity assay; flow cytometry; fungus; gene expression; health care personnel; hepatitis A; hepatitis B; hepatitis C; human; human cell; Human immunodeficiency virus; human tissue; immunity; LNCaP cell line; male; malignant transformation; PC-3 [Human prostate carcinoma] cell line; Pi3K/Akt signaling; prostate cancer; prostate cell line; real time polymerase chain reaction; real time reverse transcription polymerase chain reaction; RNA extraction; secretome; signal transduction; Treponema pallidum; tumor cell; tumor growth; umbilical cord; umbilical cord blood; umbilical cord mesenchymal stem