Molecular Characterization of Cancer Associated Fibroblasts in Prostate Cancer

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Jun 24

PMID 35740605

Authors

Giovanni Vitale

Michele Caraglia

Volker Jung

Jorn Kamradt

Davide Gentilini

Maria Teresa Di Martino

Alessandra Dicitore

Marianna Abate

Pierosandro Tagliaferri

Annalisa Itro

Matteo Ferro

Raffaele Balsamo

Marco De Sio

Gaetano Facchini

Luca Persani

Kai Schmitt

Matthias Saar

Michael Stockle

Gerhard Unteregger

Silvia Zappavigna

Affiliations

Soon will be listed here.

Abstract

Background: Stromal components surrounding epithelial cancer cells seem to play a pivotal role during epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastases. To identify the molecular mechanisms underlying tumor-stroma interactions may yield novel therapeutic targets for prostate cancer.

Methods: Gene expression profile of prostate-cancer associated fibroblast (PCAF) and prostate non-cancer associated fibroblast (PNAF) cells isolated from radical prostatectomy was performed by Illumina, analyzed, and further processed by Ingenuity: IPA software. qRT-PCR was performed on an independent set of 17 PCAF, 12 PNAF, and 12 fibroblast cell lines derived from patients with benign prostatic hyperplasia (BPHF).

Results: Using microarray analysis, we found six upregulated genes and two downregulated genes in PCAFs compared to PNAFs. To validate microarray results, we performed qRT-PCR for the most significantly regulated genes involved in the modulation of proliferation and androgen resistance on an independent set of PNAF, PCAF, and BHPF samples. We confirmed the increased expression of SCARB1, MAPK3K1, and TGF-β as well as the decreased expression of S100A10 in PCAFs compared to PNAFs and BPHFs.

Conclusions: These results provide strong evidence that the observed changes in the gene expression profile of PCAFs can contribute to functional alteration of adjacent prostate cancer cells.

Citing Articles

NRG1 secreted by cancer-associated fibroblasts contributes to enzalutamide resistance in prostate cancer cells.

Wang C, Cao H, Sun P, Chen L, Feng Y, Gao R Am J Cancer Res. 2024; 14(10):4830-4840.

PMID: 39553203 PMC: 11560826. DOI: 10.62347/OTTR3398.

Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota.

Chen L, Xu Y, Wang Y, Ren Y, Dong X, Wu P Mol Cancer. 2024; 23(1):229.

PMID: 39395984 PMC: 11470719. DOI: 10.1186/s12943-024-02137-1.

MacroH2A1.1 as a crossroad between epigenetics, inflammation and metabolism of mesenchymal stromal cells in myelodysplastic syndromes.

Giallongo C, Dulcamare I, Giallongo S, Duminuco A, Pieragostino D, Cufaro M Cell Death Dis. 2023; 14(10):686.

PMID: 37852977 PMC: 10584900. DOI: 10.1038/s41419-023-06197-x.

Cancer-Associated Fibroblast Heterogeneity, Activation and Function: Implications for Prostate Cancer.

Owen J, Clayton A, Pearson H Biomolecules. 2023; 13(1).

PMID: 36671452 PMC: 9856041. DOI: 10.3390/biom13010067.

References

Gordon J, Noble J, Midha A, Derakhshan F, Wang G, Adomat H . Upregulation of Scavenger Receptor B1 Is Required for Steroidogenic and Nonsteroidogenic Cholesterol Metabolism in Prostate Cancer. Cancer Res. 2019; 79(13):3320-3331. PMC: 6606386. DOI: 10.1158/0008-5472.CAN-18-2529. View

Matsumura Y, Ito Y, Mezawa Y, Sulidan K, Daigo Y, Hiraga T . Stromal fibroblasts induce metastatic tumor cell clusters via epithelial-mesenchymal plasticity. Life Sci Alliance. 2019; 2(4). PMC: 6653778. DOI: 10.26508/lsa.201900425. View

Bacolod M, Barany F . A Unified Transcriptional, Pharmacogenomic, and Gene Dependency Approach to Decipher the Biology, Diagnostic Markers, and Therapeutic Targets Associated with Prostate Cancer Metastasis. Cancers (Basel). 2021; 13(20). PMC: 8534121. DOI: 10.3390/cancers13205158. View

Niu Y, Xia S . Stroma-epithelium crosstalk in prostate cancer. Asian J Androl. 2008; 11(1):28-35. PMC: 3735213. DOI: 10.1038/aja.2008.39. View

Franco O, Hayward S . Targeting the tumor stroma as a novel therapeutic approach for prostate cancer. Adv Pharmacol. 2012; 65:267-313. DOI: 10.1016/B978-0-12-397927-8.00009-9. View

Zhang G, Liu Y, Yang J, Wang H, Xing Z . Inhibition of circ_0081234 reduces prostate cancer tumor growth and metastasis via the miR-1/MAP 3 K1 axis. J Gene Med. 2021; 24(8):e3376. DOI: 10.1002/jgm.3376. View

Bonollo F, Thalmann G, Kruithof-de Julio M, Karkampouna S . The Role of Cancer-Associated Fibroblasts in Prostate Cancer Tumorigenesis. Cancers (Basel). 2020; 12(7). PMC: 7409163. DOI: 10.3390/cancers12071887. View

Orr B, Riddick A, Stewart G, Anderson R, Franco O, Hayward S . Identification of stromally expressed molecules in the prostate by tag-profiling of cancer-associated fibroblasts, normal fibroblasts and fetal prostate. Oncogene. 2011; 31(9):1130-42. PMC: 3307063. DOI: 10.1038/onc.2011.312. View

Nurmik M, Ullmann P, Rodriguez F, Haan S, Letellier E . In search of definitions: Cancer-associated fibroblasts and their markers. Int J Cancer. 2019; 146(4):895-905. PMC: 6972582. DOI: 10.1002/ijc.32193. View

10.

Chen X, Song E . Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2018; 18(2):99-115. DOI: 10.1038/s41573-018-0004-1. View

11.

Noye T, Lokman N, Oehler M, Ricciardelli C . S100A10 and Cancer Hallmarks: Structure, Functions, and its Emerging Role in Ovarian Cancer. Int J Mol Sci. 2018; 19(12). PMC: 6321037. DOI: 10.3390/ijms19124122. View

12.

Kojima Y, Acar A, Eaton E, Mellody K, Scheel C, Ben-Porath I . Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A. 2010; 107(46):20009-14. PMC: 2993333. DOI: 10.1073/pnas.1013805107. View

13.

Broggi G, Lo Giudice A, DI Mauro M, Pricoco E, Piombino E, Ferro M . Insulin signaling, androgen receptor and PSMA immunohistochemical analysis by semi-automated tissue microarray in prostate cancer with diabetes (DIAMOND study). Transl Res. 2021; 238:25-35. DOI: 10.1016/j.trsl.2021.07.002. View

14.

Barron D, Rowley D . The reactive stroma microenvironment and prostate cancer progression. Endocr Relat Cancer. 2012; 19(6):R187-204. PMC: 3716392. DOI: 10.1530/ERC-12-0085. View

15.

Zheng S, Zou Y, Tang Y, Yang A, Liang J, Wu L . Landscape of cancer-associated fibroblasts identifies the secreted biglycan as a protumor and immunosuppressive factor in triple-negative breast cancer. Oncoimmunology. 2022; 11(1):2020984. PMC: 8741292. DOI: 10.1080/2162402X.2021.2020984. View

16.

Alqahtani S, Wei C, Zhang Y, Szewczyk-Bieda M, Wilson J, Huang Z . Prediction of prostate cancer Gleason score upgrading from biopsy to radical prostatectomy using pre-biopsy multiparametric MRI PIRADS scoring system. Sci Rep. 2020; 10(1):7722. PMC: 7205887. DOI: 10.1038/s41598-020-64693-y. View

17.

Traughber C, Opoku E, Brubaker G, Major J, Lu H, Lorkowski S . Uptake of high-density lipoprotein by scavenger receptor class B type 1 is associated with prostate cancer proliferation and tumor progression in mice. J Biol Chem. 2020; 295(24):8252-8261. PMC: 7294086. DOI: 10.1074/jbc.RA120.013694. View

18.

Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M . Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015; 47(4):320-9. DOI: 10.1038/ng.3225. View

19.

Zhao H, Ramos C, Brooks J, Peehl D . Distinctive gene expression of prostatic stromal cells cultured from diseased versus normal tissues. J Cell Physiol. 2006; 210(1):111-21. PMC: 2732006. DOI: 10.1002/jcp.20828. View

20.

Costa A, Kieffer Y, Scholer-Dahirel A, Pelon F, Bourachot B, Cardon M . Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer. Cancer Cell. 2018; 33(3):463-479.e10. DOI: 10.1016/j.ccell.2018.01.011. View