IL-1β inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization.

Nature Cell Biology
Zafira CastañoSandra S McAllister

Abstract

Lack of insight into mechanisms governing breast cancer metastasis has precluded the development of curative therapies. Metastasis-initiating cancer cells (MICs) are uniquely equipped to establish metastases, causing recurrence and therapeutic resistance. Using various metastasis models, we discovered that certain primary tumours elicit a systemic inflammatory response involving interleukin-1β (IL-1β)-expressing innate immune cells that infiltrate distant MIC microenvironments. At the metastatic site, IL-1β maintains MICs in a ZEB1-positive differentiation state, preventing MICs from generating highly proliferative E-cadherin-positive progeny. Thus, when the inherent plasticity of MICs is impeded, overt metastases cannot be established. Ablation of the pro-inflammatory response or inhibition of the IL-1 receptor relieves the differentiation block and results in metastatic colonization. Among patients with lymph node-positive breast cancer, high primary tumour IL-1β expression is associated with better overall survival and distant metastasis-free survival. Our data reveal complex interactions that occur between primary tumours and disseminated MICs that could be exploited to improve patient survival.

References

Aug 3, 2002·Nature Reviews. Cancer·Ann F ChambersIan C MacDonald
Jan 4, 2003·Nature Reviews. Immunology·Siamon Gordon
Sep 1, 2005·Clinical & Experimental Metastasis·Alexander D BorowskyJeffrey P Gregg
Apr 22, 2006·Contributions to Microbiology·Karin E de Visser, Lisa M Coussens
Apr 12, 2008·Nature Reviews. Cancer·Klaus PantelBurkhard Brandt
Jun 17, 2008·Cell·Sandra S McAllisterRobert A Weinberg
Jun 20, 2008·Clinical & Experimental Metastasis·George N NaumovOddbjorn Straume
Mar 24, 2009·Annual Review of Immunology·Charles A Dinarello
Mar 25, 2009·Nature Reviews. Cancer·Christoph A Klein
May 16, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Satish L DeshmaneBassel E Sawaya
Nov 26, 2009·Nature Cell Biology·Ulrich WellnerThomas Brabletz
Apr 28, 2010·Cancer Metastasis Reviews·Charles A Dinarello
Jan 27, 2011·The Journal of Clinical Investigation·Moshe ElkabetsSandra S McAllister
Mar 30, 2011·PloS One·Markus RingnérJohan Staaf
Apr 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Christine L ChafferRobert A Weinberg
Jul 26, 2011·Nature Reviews. Immunology·Alberto MantovaniSébastien Jaillon
Sep 13, 2011·Cancer Cell·Zvi GranotRobert Benezra
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He
Aug 24, 2012·Bioinformatics·Fernando García-AlcaldeAna Conesa
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
May 22, 2013·Cancer Discovery·Zafira CastañoSandra S McAllister
Jul 13, 2013·Journal of Internal Medicine·A J Redig, S S McAllister
Dec 18, 2013·Immunity·Cecilia GarlandaAlberto Mantovani
Aug 2, 2014·Nature Cell Biology·Sandra S McAllister, Robert A Weinberg
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Mar 25, 2015·Nature Reviews. Cancer·Cyrus M Ghajar
Apr 11, 2015·Cancer Cell·Brian Ruffell, Lisa M Coussens
May 20, 2015·Nature·Veronica FinisguerraMassimiliano Mazzone
May 30, 2015·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ying HuFeng Chen
Oct 7, 2015·Trends in Cell Biology·Xin Ye, Robert A Weinberg
Oct 10, 2015·Cell·Giovanni CirielloCharles M Perou

❮ Previous
Next ❯

Citations

Apr 27, 2019·The Journal of Experimental Medicine·Birgit Ritter, Florian R Greten
Nov 2, 2019·Nature Reviews. Cancer·Elizabeth D WilliamsErik W Thompson
Oct 19, 2019·Cancers·Beatriz P San JuanChristine L Chaffer
Feb 27, 2020·Journal for Immunotherapy of Cancer·David AllardJohn Stagg
May 29, 2020·Science Translational Medicine·Lin ZhangDihua Yu
Jul 3, 2019·Nature Cell Biology·Michalina JaniszewskaKornelia Polyak
May 15, 2019·Journal of Clinical Medicine·Gray W Pearson
Jan 4, 2019·Journal of Biological Engineering·Shantanu PradhanJohn H Slater
Jan 4, 2020·Development·Alan Y Wong, Jessica L Whited
May 10, 2019·Frontiers in Oncology·Ginevra DoglioniSarah-Maria Fendt
Jun 25, 2019·Frontiers in Immunology·Kevin J BakerElizabeth Brint
Jul 9, 2020·Cancers·Cédric Rébé, François Ghiringhelli
Oct 13, 2020·Frontiers in Oncology·Máté KissDamya Laoui
Feb 27, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Heidi A HansonNicola J Camp
Jan 5, 2021·Medical Oncology·Jamal Majidpoor, Keywan Mortezaee
Jan 21, 2021·Nature Reviews. Clinical Oncology·Jiajie HouBeicheng Sun
Oct 13, 2019·Cancer Letters·Yuanyuan Jiang, Hanxiang Zhan
Feb 7, 2021·Nature Reviews. Cancer·Arthur W Lambert, Robert A Weinberg
Dec 20, 2020·Cancers·Stephanie AnnettTracy Robson
Feb 4, 2021·Cancers·Adrian GottschlichSebastian Kobold
Mar 10, 2021·NPJ Precision Oncology·Jeong-Hoon JangYoung-Joon Surh
Nov 7, 2020·International Journal of Molecular Sciences·Marta ChiavariLucia Lisi
Mar 16, 2021·The Journal of Clinical Investigation·Aaron M MuscarellaXiang H-F Zhang
Apr 13, 2021·Journal of Biomedical Science·Sara Socorro FariaKelly Grace Magalhães
Jun 5, 2021·Nature Reviews. Cancer·Daria BriukhovetskaSebastian Kobold
Jun 3, 2021·International Journal of Molecular Sciences·Sana HibinoKoji Taniguchi
Oct 17, 2020·Journal of Hematology & Oncology·Julia López de AndrésJuan Antonio Marchal
Oct 31, 2021·Journal for Immunotherapy of Cancer·Chenghui YangJian Huang

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE111157
GSE55633

Methods Mentioned

BETA
xenografts
protein-folding
xenograft
PCR
RNA-seq
flow cytometry
ELISAs
Antibody Array
fluorescence-activated cell sorting
Assay

Software Mentioned

HMLER
GSEA
bcbioRNASeq R
FACSDiva
TreeStar
MultiQC
FastQC
FlowJo
clusterProfiler
Salmon

Related Concepts

Related Feeds

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Related Papers

Nature Reviews. Cancer
Patricia S Steeg
Genes & Development
Toni Celià-Terrassa, Yibin Kang
Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
Anke H van der PloegLutz Hamann
© 2022 Meta ULC. All rights reserved