Proteomic profiling of human prostate cancer-associated fibroblasts identifies LOXL2 promotes tumour migration in the extracellular matrix
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cell Culture, Fibroblast
DISEASE(S): Prostate Adenocarcinoma
SUBMITTER: 
Elizabeth Nguyen
LAB HEAD: Roger Daly
PROVIDER: PXD010611 | Pride | 2019-05-24
REPOSITORIES: Pride
Publications
Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment.
Nguyen Elizabeth V EV Pereira Brooke A BA Lawrence Mitchell G MG Ma Xiuquan X Rebello Richard J RJ Chan Howard H Niranjan Birunthi B Wu Yunjian Y Ellem Stuart S Guan Xiaoqing X Wu Jianmin J Skhinas Joanna N JN Cox Thomas R TR Risbridger Gail P GP Taylor Renea A RA Lister Natalie L NL Daly Roger J RJ
Molecular & cellular proteomics : MCP 20190506 7
In prostate cancer, cancer-associated fibroblasts (CAF) exhibit contrasting biological properties to non-malignant prostate fibroblasts (NPF) and promote tumorigenesis. Resolving intercellular signaling pathways between CAF and prostate tumor epithelium may offer novel opportunities for research translation. To this end, the proteome and phosphoproteome of four pairs of patient-matched CAF and NPF were characterized to identify discriminating proteomic signatures. Samples were analyzed by liquid ...[more]
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Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF?-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. 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