Unbiased differential proteomic profiling between cancer-associated fibroblasts and cancer cell lines.

Autor: Lau R; Clinical Pharmacology and Adaptive Therapy Group, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 15 Cotswold Road, London SM2 5NG, United Kingdom. Electronic address: rachel.lau@icr.ac.uk., Yu L; Functional Proteomics group, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom., Roumeliotis TI; Functional Proteomics group, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom., Stewart A; Clinical Pharmacology and Adaptive Therapy Group, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 15 Cotswold Road, London SM2 5NG, United Kingdom., Pickard L; Clinical Pharmacology and Adaptive Therapy Group, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 15 Cotswold Road, London SM2 5NG, United Kingdom., Riisanes R; Cancer Biomarkers Group, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 15 Cotswold Road, London SM2 5NG, United Kingdom., Gurel B; Cancer Biomarkers Group, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 15 Cotswold Road, London SM2 5NG, United Kingdom., de Bono JS; Cancer Biomarkers Group, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 15 Cotswold Road, London SM2 5NG, United Kingdom., Choudhary JS; Functional Proteomics group, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom. Electronic address: jyoti.choudhary@icr.ac.uk., Banerji U; Clinical Pharmacology and Adaptive Therapy Group, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 15 Cotswold Road, London SM2 5NG, United Kingdom. Electronic address: udai.banerji@icr.ac.uk.
Jazyk: angličtina
Zdroj: Journal of proteomics [J Proteomics] 2023 Sep 30; Vol. 288, pp. 104973. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1016/j.jprot.2023.104973
Abstrakt: Cancer-associated fibroblasts (CAFs) are a key component of tumors. We aimed to profile the proteome of cancer cell lines representing three common cancer types (lung, colorectal and pancreatic) and a representative CAF cell line from each tumor type to gain insight into CAF function and novel CAF biomarkers. We used isobaric labeling, liquid chromatography and mass spectrometry to evaluate the proteome of 9 cancer and 3 CAF cell lines. Of the 9460 proteins evaluated, functional enrichment analysis revealed an upregulation of N-glycan biosynthesis and extracellular matrix proteins in CAFs. 85 proteins had 16-fold higher expression in CAFs compared to cancer cells, including previously known CAF markers like fibroblast activation protein (FAP). Novel overexpressed CAF biomarkers included heat shock protein β-6 (HSPB6/HSP20) and cyclooxygenase 1 (PTGS1/COX1). SiRNA knockdown of the genes encoding these proteins did not reduce contractility in lung CAFs, suggesting they were not crucial to this function. Immunohistochemical analysis of 30 tumor samples (10 lung, 10 colorectal and 10 pancreatic) showed restricted HSPB6 and PTGS1 expression in the stroma. Therefore, we describe an unbiased differential proteome analysis of CAFs compared to cancer cells, which revealed higher expression of HSPB6 and PTGS1 in CAFs. Data are available via ProteomeXchange (PXD040360). SIGNIFICANCE: Cancer-associated fibroblasts (CAFs) are highly abundant stromal cells present in tumors. CAFs are known to influence tumor progression and drug resistance. Characterizing the proteome of CAFs could give potential insights into new stromal drug targets and biomarkers. Mass spectrometry-based analysis comparing proteomic profiles of CAFs and cancers characterized 9460 proteins of which 85 proteins had 16-fold higher expression in CAFs compared to cancer cells. Further interrogation of this rich resource could provide insight into the function of CAFs and could reveal putative stromal targets. We describe for the first time that heat shock protein β-6 (HSPB6/HSP20) and cyclooxygenase 1 (PTGS1/COX1) are overexpressed in CAFs compared to cancer cells.
Competing Interests: Declaration of Competing Interest All authors are an employee of The Institute of Cancer Research, which has commercial interest in abiraterone and PARP inhibition in DNA repair defective cancers and the development of HSP90, PI3K, HDAC, AKT, ROCK, RAF, CHK1, MPS-1 and HSF-1 inhibitors. (no personal income). J.B has served on advisory boards and received fees from companies including Amgen, AstraZeneca, Astellas, Bayer, Bioxcel Therapeutics, Daiichi, Genentech/Roche, GSK, Harpoon, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Pfizer, Sanofi Aventis. J.B has also received funding or other support from AstraZeneca, Astellas, Bayer, Cellcentric, Daiichi, Genentech, Genmab, GSK, Janssen, Merck Serono, MSD, Menarini/Silicon Biosystems, Orion, Sanofi Aventis, Sierra Oncology, Taiho, Pfizer, Vertex. J.B was named as an inventor, with no financial interest for patent 8,822,438, submitted by Janssen that covers the use of abiraterone acetate with corticosteroids. J.B has been the CI/PI of many industry sponsored clinical trials. U.B has served on advisory boards and received fees from companies including Carrick Therapeutics and Pegasy. U.B has received grants from Avacta, BTG international, Verastem, Carrick Therapeutics and Chugai.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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