IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40688-x.html
   My bibliography  Save this article

An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver

Author

Listed:
  • Carlos Fernández Moro

    (Karolinska Institutet
    Karolinska University Hospital
    Karolinska Institutet)

  • Natalie Geyer

    (Karolinska Institutet)

  • Sara Harrizi

    (Karolinska Institutet)

  • Yousra Hamidi

    (Karolinska Institutet)

  • Sara Söderqvist

    (Karolinska Institutet)

  • Danyil Kuznyecov

    (Skåne University Hospital)

  • Evelina Tidholm Qvist

    (Karolinska University Hospital)

  • Media Salmonson Schaad

    (Karolinska Institutet)

  • Laura Hermann

    (Karolinska Institutet)

  • Amanda Lindberg

    (Uppsala University)

  • Rainer L. Heuchel

    (Karolinska Institutet)

  • Alfonso Martín-Bernabé

    (Karolinska Institutet)

  • Soniya Dhanjal

    (Karolinska Institutet)

  • Anna C. Navis

    (Karolinska Institutet)

  • Christina Villard

    (Karolinska Institutet)

  • Andrea C. Valle

    (Karolinska Institutet)

  • Lorand Bozóky

    (Karolinska Institutet)

  • Ernesto Sparrelid

    (Karolinska Institutet, Karolinska University Hospital)

  • Luc Dirix

    (Translational Cancer Research Unit (GZA Hospitals and University of Antwerp))

  • Carina Strell

    (Uppsala University
    University of Bergen)

  • Arne Östman

    (Karolinska Institutet)

  • Bernhard Schmierer

    (Karolinska Institutet)

  • Peter B. Vermeulen

    (Translational Cancer Research Unit (GZA Hospitals and University of Antwerp))

  • Jennie Engstrand

    (Karolinska Institutet, Karolinska University Hospital)

  • Béla Bozóky

    (Karolinska University Hospital)

  • Marco Gerling

    (Karolinska Institutet
    Theme Cancer, Karolinska University Hospital, 17 176)

Abstract

A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule’s extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFRhigh stroma at the liver edge to FAPhigh stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.

Suggested Citation

  • Carlos Fernández Moro & Natalie Geyer & Sara Harrizi & Yousra Hamidi & Sara Söderqvist & Danyil Kuznyecov & Evelina Tidholm Qvist & Media Salmonson Schaad & Laura Hermann & Amanda Lindberg & Rainer L., 2023. "An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40688-x
    DOI: 10.1038/s41467-023-40688-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40688-x
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-40688-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Eiman Azim & Juan Jiang & Bror Alstermark & Thomas M. Jessell, 2014. "Skilled reaching relies on a V2a propriospinal internal copy circuit," Nature, Nature, vol. 508(7496), pages 357-363, April.
    2. P. Ramachandran & R. Dobie & J. R. Wilson-Kanamori & E. F. Dora & B. E. P. Henderson & N. T. Luu & J. R. Portman & K. P. Matchett & M. Brice & J. A. Marwick & R. S. Taylor & M. Efremova & R. Vento-Tor, 2019. "Resolving the fibrotic niche of human liver cirrhosis at single-cell level," Nature, Nature, vol. 575(7783), pages 512-518, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. LiangYu Zhao & Sha Han & HengChuan Su & JianYing Li & ErLei Zhi & Peng Li & ChenCheng Yao & RuHui Tian & HuiXing Chen & HuiRong Chen & JiaQiang Luo & ChenKun Shi & ZhiYong Ji & JianLin Hu & Gang Wu & , 2022. "Single-cell transcriptome atlas of the human corpus cavernosum," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. T. Hautz & S. Salcher & M. Fodor & G. Sturm & S. Ebner & A. Mair & M. Trebo & G. Untergasser & S. Sopper & B. Cardini & A. Martowicz & J. Hofmann & S. Daum & M. Kalb & T. Resch & F. Krendl & A. Weisse, 2023. "Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Yi Duan & Huikuan Chu & Katharina Brandl & Lu Jiang & Suling Zeng & Nairika Meshgin & Eleni Papachristoforou & Josepmaria Argemi & Beatriz G. Mendes & Yanhan Wang & Hua Su & Weizhong Sun & Cristina Ll, 2021. "CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Adriana A. de Jesus & Guibin Chen & Dan Yang & Tomas Brdicka & Natasha M. Ruth & David Bennin & Dita Cebecauerova & Hana Malcova & Helen Freeman & Neil Martin & Karel Svojgr & Murray H. Passo & Farzan, 2023. "Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Meirion Raymant & Yuliana Astuti & Laura Alvaro-Espinosa & Daniel Green & Valeria Quaranta & Gaia Bellomo & Mark Glenn & Vatshala Chandran-Gorner & Daniel H. Palmer & Christopher Halloran & Paula Ghan, 2024. "Macrophage-fibroblast JAK/STAT dependent crosstalk promotes liver metastatic outgrowth in pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    6. Anna Podleśny-Drabiniok & Gloriia Novikova & Yiyuan Liu & Josefine Dunst & Rose Temizer & Chiara Giannarelli & Samuele Marro & Taras Kreslavsky & Edoardo Marcora & Alison Mary Goate, 2024. "BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer’s disease and other disorders of lipid-rich tissues," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    7. Han-Ying Huang & Yan-Zhou Chen & Chuang Zhao & Xin-Nan Zheng & Kai Yu & Jia-Xing Yue & Huai-Qiang Ju & Yan-Xia Shi & Lin Tian, 2024. "Alternations in inflammatory macrophage niche drive phenotypic and functional plasticity of Kupffer cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Daniel J. Butler & Alexander P. Keim & Shantanu Ray & Eiman Azim, 2023. "Large-scale capture of hidden fluorescent labels for training generalizable markerless motion capture models," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Yuichi Tsuchiya & Takao Seki & Kenta Kobayashi & Sachiko Komazawa-Sakon & Shigeyuki Shichino & Takashi Nishina & Kyoko Fukuhara & Kenichi Ikejima & Hidenari Nagai & Yoshinori Igarashi & Satoshi Ueha &, 2023. "Fibroblast growth factor 18 stimulates the proliferation of hepatic stellate cells, thereby inducing liver fibrosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    10. Dan-Pei Li & Li Huang & Ran-Ran Kan & Xiao-Yu Meng & Shu-Yun Wang & Hua-Jie Zou & Ya-Ming Guo & Pei-Qiong Luo & Li-Meng Pan & Yu-Xi Xiang & Bei-Bei Mao & Yu-Yu Xie & Zhi-Han Wang & Min Yang & Rui He &, 2023. "LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Caitriona M. McEvoy & Julia M. Murphy & Lin Zhang & Sergi Clotet-Freixas & Jessica A. Mathews & James An & Mehran Karimzadeh & Delaram Pouyabahar & Shenghui Su & Olga Zaslaver & Hannes Röst & Rangi Ar, 2022. "Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    12. Ting Dong & Guangan Hu & Zhongqi Fan & Huirui Wang & Yinghui Gao & Sisi Wang & Hao Xu & Michael B. Yaffe & Matthew G. Vander Heiden & Guoyue Lv & Jianzhu Chen, 2024. "Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    13. Mayra Cruz Tleugabulova & Sandra P. Melo & Aaron Wong & Alexander Arlantico & Meizi Liu & Joshua D. Webster & Julia Lau & Antonie Lechner & Basak Corak & Jonathan J. Hodgins & Venkata S. Garlapati & M, 2024. "Induction of a distinct macrophage population and protection from lung injury and fibrosis by Notch2 blockade," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Hui Xia & Catherine R. Dufour & Younes Medkour & Charlotte Scholtes & Yonghong Chen & Christina Guluzian & Wafa B’chir & Vincent Giguère, 2023. "Hepatocyte FBXW7-dependent activity of nutrient-sensing nuclear receptors controls systemic energy homeostasis and NASH progression in male mice," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
    15. Mindy K. Graham & Rulin Wang & Roshan Chikarmane & Bulouere Abel & Ajay Vaghasia & Anuj Gupta & Qizhi Zheng & Jessica Hicks & Polina Sysa-Shah & Xin Pan & Nicole Castagna & Jianyong Liu & Jennifer Mey, 2024. "Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    16. Yuan Guan & Annika Enejder & Meiyue Wang & Zhuoqing Fang & Lu Cui & Shih-Yu Chen & Jingxiao Wang & Yalun Tan & Manhong Wu & Xinyu Chen & Patrik K. Johansson & Issra Osman & Koshi Kunimoto & Pierre Rus, 2021. "A human multi-lineage hepatic organoid model for liver fibrosis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    17. Michael T. H. Ng & Rowie Borst & Hamez Gacaferi & Sarah Davidson & Jessica E. Ackerman & Peter A. Johnson & Caio C. Machado & Ian Reekie & Moustafa Attar & Dylan Windell & Mariola Kurowska-Stolarska &, 2024. "A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    18. Morgane Mabire & Pushpa Hegde & Adel Hammoutene & Jinghong Wan & Charles Caër & Rola Al Sayegh & Mathilde Cadoux & Manon Allaire & Emmanuel Weiss & Tristan Thibault-Sogorb & Olivier Lantz & Michèle Go, 2023. "MAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40688-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.