Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells

Molecular Oncology
Thomas KryzaJudith A Clements

Abstract

The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line, including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease-activated receptor-1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient-de...Continue Reading

References

Jan 30, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yong-Jun YinRachel Bar-Shavit
Mar 15, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Yong-Jun YinRachel Bar-Shavit
Mar 28, 2006·The American Journal of Pathology·Marinella HolzhausenNathalie Vergnolle
Apr 25, 2007·Critical Reviews in Clinical Laboratory Sciences·M ChrisofosC Deliveliotis
Sep 8, 2007·The Journal of Biological Chemistry·Hyesook YoonMichael Blaber
Dec 17, 2008·Cancer Chemotherapy and Pharmacology·Flaubert Mbeunkui, Donald J Johann
Oct 2, 2009·International Journal of Cancer. Journal International Du Cancer·Wenbin WangThomas K Takayama
Jan 15, 2011·Trends in Cell Biology·Steven D Mason, Johanna A Joyce
Nov 1, 2011·Expert Opinion on Investigational Drugs·Andreas VarkarisGary E Gallick
Jan 4, 2012·Nature Reviews. Drug Discovery·Rithwik RamachandranMorley D Hollenberg
Aug 1, 2012·Oncology Letters·Na HanLisong Teng
Sep 25, 2012·European Urology·Zoran Culig
Apr 6, 2013·Nature Protocols·Mitchell G LawrenceGail P Risbridger
Jun 19, 2013·Trends in Molecular Medicine·Shalom MadarVarda Rotter
Oct 30, 2013·The Prostate·George S KaragiannisEleftherios P Diamandis
Jan 11, 2014·Seminars in Cancer Biology·Olivier De WeverMarc Bracke
Jan 31, 2014·Expert Review of Proteomics·Monika DvorakovaPavel Bouchal
May 2, 2014·Cancer Research·Francesca BruzzeseMartin Augsten
Jul 1, 2014·Cancers·Kim De VeirmanKarin Vanderkerken
Feb 24, 2015·Nature Reviews. Drug Discovery·Ioannis PrassasEleftherios P Diamandis

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Citations

Aug 18, 2018·Expert Opinion on Therapeutic Targets·Daniela LoessnerViktor Magdolen
Jul 17, 2020·Cancers·Francesco BonolloSofia Karkampouna
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Jenniffer LinaresAlexandre Calon
Aug 11, 2021·Scientific Reports·Eitan RabinovitchNiv Papo

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Methods Mentioned

BETA
ELISA
transfection
PCR
ELISAs
Profiler
biopsy
SMA
protein array
DNA assay
biopsies

Software Mentioned

GraphPad
InCell analyzer
imageJ
cellprofiler
GraphPad Prism

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