title: The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages.
abstract: Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Andersson
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Hosaka
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Renhai
authors.initials: R
authors.lastname: Cao
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Hideki
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Xiaojuan
authors.identifier: 0000-0002-5789-7571
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: The TCM Hospital of Zhejiang Province, Hangzhou, Zhejiang 310006, China.
authors.forename: Rujie
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: Unit of Computational Medicine, Department of Medicine, Center for Molecular Medicine, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Hiromasa
authors.identifier: 0000-0002-6793-5885
authors.initials: H
authors.lastname: Morikawa
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.|Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium.|Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center VIB, B-9052 Ghent, Belgium.
authors.forename: Harald
authors.initials: H
authors.lastname: Braun
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium.|Unit of Molecular Signal Transduction in Inflammation, Inflammation Research Center VIB, B-9052 Ghent, Belgium.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
authors.forename: Nilesh
authors.initials: N
authors.lastname: Samani
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.affiliation: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Emily
authors.initials: E
authors.lastname: Hams
authors.affiliation: Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, 2200N Copenhagen, Denmark.
authors.forename: Steen
authors.identifier: 0000-0002-0741-907X
authors.initials: S
authors.lastname: Dissing
authors.affiliation: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77 Stockholm, Sweden.|Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.|Department of Medicine and Health Sciences, Linköping University, 581 83 Linköping, Sweden.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D000077214:Becaplermin; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020286:Pericytes / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D000067596:Interleukin-33; D020574:Proto-Oncogene Proteins c-sis; C484456:SOX7 protein, human; D055760:SOXF Transcription Factors; D000077214:Becaplermin