Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer.
Joakin O MoriIsra ElhussinW Nathaniel BrennenMindy K GrahamTamara L LotanClayton C YatesAngelo M DeMarzoSamuel R DenmeadeSrinivasan YegnasubramanianWilliam G NelsonGerald V DenisElizabeth A PlatzAlan K MeekerChristopher M HeaphyPublished in: Nature reviews. Urology (2023)
The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.
Keyphrases
- prostate cancer
- extracellular matrix
- radical prostatectomy
- induced apoptosis
- endothelial cells
- stem cells
- cell cycle arrest
- oxidative stress
- bone marrow
- signaling pathway
- squamous cell carcinoma
- small cell lung cancer
- endoplasmic reticulum stress
- cell cycle
- cell death
- benign prostatic hyperplasia
- cancer therapy
- squamous cell
- free survival
- anti inflammatory