Identification of functional and diverse circulating cancer-associated fibroblasts in metastatic castration-naïve prostate cancer patients.
Richell BooijinkLeon W M M TerstappenEshwari DathathriKhrystany T IsebiaJaco KraanJohn W M MartensRuchi BansalPublished in: Molecular oncology (2024)
In prostate cancer (PCa), cancer-associated fibroblasts (CAFs) promote tumor progression, drug resistance, and metastasis. Although circulating tumor cells are studied as prognostic and diagnostic markers, little is known about other circulating cells and their association with PCa metastasis. Here, we explored the presence of circulating CAFs (cCAFs) in metastatic castration-naïve prostate cancer (mCNPC) patients. cCAFs were stained with fibroblast activation protein (FAP), epithelial cell adhesion molecule (EpCAM), and receptor-type tyrosine-protein phosphatase C (CD45), then FAP + EpCAM - cCAFs were enumerated and sorted using fluorescence-activated cell sorting. FAP + EpCAM - cCAFs ranged from 60 to 776 (389 mean ± 229 SD) per 2 × 10 8 mononuclear cells, whereas, in healthy donors, FAP + EpCAM - cCAFs ranged from 0 to 71 (28 mean ± 22 SD). The mCNPC-derived cCAFs showed positivity for vimentin and intracellular collagen-I. They were viable and functional after sorting, as confirmed by single-cell collagen-I secretion after 48 h of culturing. Two cCAF subpopulations, FAP + CD45 - and FAP + CD45 + , were identified, both expressing collagen-I and vimentin, but with distinctly different morphologies. Collectively, this study demonstrates the presence of functional and viable circulating CAFs in mCNPC patients, suggesting the role of these cells in prostate cancer.
Keyphrases
- prostate cancer
- circulating tumor cells
- cell adhesion
- induced apoptosis
- end stage renal disease
- single cell
- radical prostatectomy
- cell cycle arrest
- ejection fraction
- chronic kidney disease
- newly diagnosed
- squamous cell carcinoma
- small cell lung cancer
- peritoneal dialysis
- binding protein
- patient reported outcomes
- mesenchymal stem cells
- extracellular matrix
- peripheral blood
- poor prognosis
- cell proliferation
- bone marrow
- high throughput
- kidney transplantation
- wild type