Proteomic characterisation of prostate cancer intercellular communication reveals cell type-selective signalling and TMSB4X-dependent fibroblast reprogramming.

Wu Y, Clark KC, Nguyen EV, Niranjan B, Horvath LG, Taylor RA, Daly RJ

Cellular oncology (Dordrecht, Netherlands)28 Sept 2022Cited by 7 (Europe PMC)

PMID36169805PMCIDPMC9747870DOI10.1007/s13402-022-00719-zPepBankPUB-36169805

Summary

BackgroundIn prostate cancer, the tumour microenvironment (TME) represents an important regulator of disease progression and response to treatment. In the TME, cancer-associated fibroblasts (CAFs) play a key role in tumour progression, however the mechanisms underpinning fibroblast-cancer cell interactions are incompletely resolved. Here, we address this by applying cell type-specific labelling with amino acid precursors (CTAP) and mass spectrometry (MS)-based (phospho)proteomics to prostate cancer for the first time.MethodsReciprocal interactions between PC3 prostate cancer cells co-cultured with WPMY-1 prostatic fibroblasts were characterised using CTAP-MS. Signalling network changes were determined using Metascape and Enrichr and visualised using Cytoscape. Thymosin β4 (TMSB4X) overexpression was achieved via retroviral transduction and assayed by ELISA. Cell motility was determined using Transwell and random cell migration assays and expression of CAF markers by indirect immunofluorescence.ResultsWPMY-1 cells co-cultured with PC3s demonstrated a CAF-like phenotype, characterised by enhanced PDGFRB expression and alterations in signalling pathways regulating epithelial-mesenchymal transition, cytoskeletal organisation and cell polarisation. In contrast, co-cultured PC3 cells exhibited more modest network changes, with alterations in mTORC1 signalling and regulation of the actin cytoskeleton. The expression of the actin binding protein TMSB4X was significantly decreased in co-cultured WPMY-1 fibroblasts, and overexpression of TMSB4X in fibroblasts decreased migration of co-cultured PC3 cells, reduced fibroblast motility, and protected the fibroblasts from being educated to a CAF-like phenotype by prostate cancer cells.ConclusionsThis study highlights the potential of CTAP-MS to characterise intercellular communication within the prostate TME and identify regulators of cellular crosstalk such as TMSB4X.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

No result from this study comes from a test of the peptide.

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01LabEndogenous levelIn vitro (cells)Mechanism
In WPMY-1 fibroblasts co-cultured with PC3 prostate cancer cells, expression of the body's own TMSB4X was significantly decreased.
In plain wordsIn cells, the body's own TMSB4X level fell in fibroblasts grown together with prostate cancer cells.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTMSB4X expression in co-cultured fibroblasts
Study
n: not reported in source
PC3 prostate cancer cells co-cultured with WPMY-1 fibroblasts
Outcome group
Tumor growth · Cancer
Source sentences
Summary
The expression of the actin binding protein TMSB4X was significantly decreased in co-cultured WPMY-1 fibroblasts
2 context sentences(design, population, supporting numbers)
Summary · context
Reciprocal interactions between PC3 prostate cancer cells co-cultured with WPMY-1 prostatic fibroblasts were characterised using CTAP-MS.
Summary · context
Thymosin β4 (TMSB4X) overexpression was achieved via retroviral transduction and assayed by ELISA.
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3616980501

Studies that did not test the peptide alone3

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

02LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In co-culture, overexpression of TMSB4X in fibroblasts decreased the migration of PC3 prostate cancer cells.
In plain wordsIn cells, raising TMSB4X in fibroblasts reduced the movement of nearby prostate cancer cells.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseMigration of co-cultured PC3 cells with fibroblast TMSB4X overexpression
Study
n: not reported in source
PC3 prostate cancer cells co-cultured with WPMY-1 fibroblasts
Outcome group
Tumor growth · Cancer
Source sentences
Summary
overexpression of TMSB4X in fibroblasts decreased migration of co-cultured PC3 cells
2 context sentences(design, population, supporting numbers)
Summary · context
Reciprocal interactions between PC3 prostate cancer cells co-cultured with WPMY-1 prostatic fibroblasts were characterised using CTAP-MS.
Summary · context
Thymosin β4 (TMSB4X) overexpression was achieved via retroviral transduction and assayed by ELISA.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3616980502
03LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
Overexpression of TMSB4X in WPMY-1 fibroblasts reduced fibroblast motility.
In plain wordsIn cells, raising TMSB4X in fibroblasts slowed fibroblast movement.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseFibroblast motility with TMSB4X overexpression
Study
n: not reported in source
PC3 prostate cancer cells co-cultured with WPMY-1 fibroblasts
Outcome group
Tumor growth · Cancer
Source sentences
Summary
reduced fibroblast motility
2 context sentences(design, population, supporting numbers)
Summary · context
Reciprocal interactions between PC3 prostate cancer cells co-cultured with WPMY-1 prostatic fibroblasts were characterised using CTAP-MS.
Summary · context
Thymosin β4 (TMSB4X) overexpression was achieved via retroviral transduction and assayed by ELISA.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3616980503
04LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
Overexpression of TMSB4X protected fibroblasts from being educated to a cancer-associated fibroblast-like phenotype by prostate cancer cells.
In plain wordsIn cells, raising TMSB4X protected fibroblasts from being turned into cancer-supporting fibroblasts by prostate cancer cells.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseFibroblast education to a CAF-like phenotype with TMSB4X overexpression
Study
n: not reported in source
PC3 prostate cancer cells co-cultured with WPMY-1 fibroblasts
Outcome group
Tumor growth · Cancer
Source sentences
Summary
protected the fibroblasts from being educated to a CAF-like phenotype by prostate cancer cells.
2 context sentences(design, population, supporting numbers)
Summary · context
Reciprocal interactions between PC3 prostate cancer cells co-cultured with WPMY-1 prostatic fibroblasts were characterised using CTAP-MS.
Summary · context
Thymosin β4 (TMSB4X) overexpression was achieved via retroviral transduction and assayed by ELISA.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-3616980504

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 01:52 UTC
Study results updated
Version 1
12 Oct 2026, 18:17 UTC
First added · source update from Europe PMC

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