Integrative characterisation of secreted factors involved in intercellular communication between prostate epithelial or cancer cells and fibroblasts
- Author(s)
- Wu, Y; Clark, KC; Niranjan, B; Chueh, AC; Horvath, LG; Taylor, RA; Daly, RJ;
- Journal Title
- Molecular Oncology
- Publication Type
- Research article
- Abstract
- Reciprocal interactions between prostate cancer cells and carcinoma-associated fibroblasts (CAFs) mediate cancer development and progression; however, our understanding of the signalling pathways mediating these cellular interactions remains incomplete. To address this, we defined secretome changes upon co-culture of prostate epithelial or cancer cells with fibroblasts that mimic bi-directional communication in tumours. Using antibody arrays, we profiled conditioned media from mono- and co-cultures of prostate fibroblasts, epithelial and cancer cells, identifying secreted proteins that are upregulated in co-culture compared to mono-culture. Six of these (CXCL10, CXCL16, CXCL6, FST, PDGFAA, IL-17B) were functionally screened by siRNA knockdown in prostate cancer cell/fibroblast co-cultures, revealing a key role for follistatin (FST), a secreted glycoprotein that binds and bioneutralises specific members of the TGF-beta superfamily, including activin A. Expression of FST by both cell types was required for the fibroblasts to enhance prostate cancer cell proliferation and migration, whereas FST knockdown in co-culture grafts decreased tumour growth in mouse xenografts. This study highlights the complexity of prostate cancer cell-fibroblast communication, demonstrates that co-culture secretomes cannot be predicted from individual cultures, and identifies FST as a tumour-microenvironment-derived secreted factor that represents a candidate therapeutic target.
- Publisher
- Wiley
- Keywords
- Male; Humans; Animals; Mice; *Prostate/pathology; Cell Communication; Fibroblasts/metabolism; Signal Transduction; Coculture Techniques; *Prostatic Neoplasms/pathology; Cell Line, Tumor; Epithelial Cells/metabolism; Tumor Microenvironment
- Department(s)
- Laboratory Research
- PubMed ID
- 36608258
- Publisher's Version
- https://doi.org/10.1002/1878-0261.13376
- Open Access at Publisher's Site
https://doi.org/10.1002/1878-0261.13376- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-06-15 07:24:58
Last Modified: 2023-06-15 07:25:48