Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

British Journal of Cancer
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. british journal of cancer
  3. regular article
  4. article
Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients
Download PDF
Download PDF
  • Regular Article
  • Open access
  • Published: 29 May 2001

Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients

  • A Scorilas1,5 nAff6,
  • A Karameris5,
  • N Arnogiannaki2,
  • A Ardavanis3,
  • P Bassilopoulos4,
  • T Trangas1 &
  • …
  • M Talieri1 

British Journal of Cancer volume 84, pages 1488–1496 (2001)Cite this article

  • 2105 Accesses

  • 205 Citations

  • Metrics details

This article has been updated

Abstract

Matrix metalloprotease-9 (MMP-9; 92 kDa type IV collaganase, gelatinase B) is regarded as, important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodelling events. In this study we evaluate the prognostic value of MMP-9, by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 status was compared with the concentration of cytosolic Cathepsin-D and with other established prognostic factors, in terms of disease free survival and overall survival. The median follow-up period was 62 months. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger (P=0.014), invasive ductal histologic (P=0.037), progesterone receptor (PR)-negative and PR-strong positive tumours (P< 0.001), as well as samples belonging to patients with stage III-IV disease (P=0.009) and age 45–55 years (P=0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR=0.45; P=0.039) or death (RR=0.32; P=0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of OS (RR=0.47; P=0.034) in node-negative but not in node-positive patients. Our results suggest that MMP-9 may be an independent favourable prognostic factor in node-negative breast cancer patients. The overexpression of MMP-9 in breast cancer may be also used as a marker to subdivide node negative breast cancer patients in order to determine the optimal treatment modality. © 2001 Cancer Research Campaign http://www.bjcancer.com

Similar content being viewed by others

Impending role of inflammatory markers and their specificity and sensitivity in breast cancer patients

Article Open access 02 July 2024

Matrix metalloproteinase 11 (MMP11) in macrophages promotes the migration of HER2-positive breast cancer cells and monocyte recruitment through CCL2–CCR2 signaling

Article 13 November 2021

Combined knockdown of CD151 and MMP9 may inhibit the malignant biological behaviours of triple-negative breast cancer through the GSK-3β/β-catenin-related pathway

Article Open access 18 September 2024

Article PDF

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Ardavanis A, Scorilas A, Amanatidou A, Gerakini F, Missitzis I, Garoufali A, Pissakas G, Pateras C, Apostolikas N, Rigatos G and Yiotis I (1997) Cathepsin-D concentration in tumour cytosols improves the accuracy of prognostic evaluation of primary breast cancer. Anticancer Res 17: 1405–1410

    CAS  PubMed  Google Scholar 

  • Bajou K, Noel A, Gerard RD, Masson V, Brunner N, Holst-Hansen Skobe M, Fusenig NE, Carmeliet P, Collen D and Foidart JM (1998) Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med 8: 923–928

    Article  Google Scholar 

  • Benaud CH, Dickson RB and Thompson EW (1998) Roles of the matrix metalloproteinases in mammary gland development and cancer. Br Cancer Res Treat 50: 97–116

    Article  CAS  Google Scholar 

  • Bianchi E, Cohen RL, Dai A, Thor AT, Shuman MA and Smith HS (1995) Immunohistochemical localization of the plasminogen activator inhibitor-1 in breast cancer. Int J Cancer 60: 597–603

    Article  CAS  PubMed  Google Scholar 

  • Blavier L and DeClerck YA (1997) Tissue inhibitor of metalloproteinases-2 is expressed in the interstitial matrix in adult mouse organs and during embryonic development. Molecular Biology of the Cell 8: 1513–1527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruner KL, Rodgers WH, Gold LI, Korc M, Hargrove JT, Matrisian LM and Osteen KG (1995) Transforming growth factor-b mediates the progesterone suppression of an epithelial metalloproteinase by adjacent stroma in the human endometrium. Proc Natl Acad Sci USA 92: 7362–7366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chambers AF and Matrisian LM (1997) Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89: 1260–1270

    Article  CAS  PubMed  Google Scholar 

  • Daidone MG, Silverstrini R, D'Errico A, Di Fronza G, Benini E, Mancini A, Garbisa S Liotta L and Grigioni W (1991) Laminin receptors, collagenase IV and prognosis in node negative breast cancers. Int J Cancer 48: 529–532

    Article  CAS  PubMed  Google Scholar 

  • Dano K, Behrendt N, Brunner N, Ellis V, Plong M and Pyke C (1994) The urokinase receptor: protein structure and the role in plasminogen activation and cancer invasion. Fibrinolysis 8: 189–203

    Article  Google Scholar 

  • Doussal VL, Tubiana-Hulin M, Friedman S, Hacerne K, Spyratos F and Brunet M (1989) Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR): an improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas. Cancer 64: 1914–1922

    Article  PubMed  Google Scholar 

  • Duffy MJ, Blaser J, Duggan C, McDermott E, O'Higgins N, Fennelly JJ and Tschesche H (1995) Assay of matrix metalloproteinases types 8 and 9 by ELISA in human breast cancer. Br J Cancer 71: 1025–1028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elashry-Stowers D, Zava D, Speers W and Edwards D (1988) Immunochytochemical localization of progesterone receptors in breast cancer with antihuman receptor monoclonal antibodies. Cancer Res 48: 6462–6474

    CAS  PubMed  Google Scholar 

  • Friedman R, Toth M and Pena D Mobashery (1995) Activation of progelatinase B (MMP-9) by gelatinase A (MMP-2). Cancer Res 55: 2548–2555

    Google Scholar 

  • Garbett EA, Reed MWR and Brown NJ (1999) Proteolysis in human breast and colorectal cancer. Br J Cancer 81: 287–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanemaaijer R, Sier C, Visser H, Scholte L, van Lent N, Toet K, Hoekman K and Verheijen J (1999) MMP-9 activity in urine from patients with various tumors, as measured by a novel MMP activity assay modified urokinase as a substrate. Ann NY Acad Sci 878: 141–149

    Article  CAS  PubMed  Google Scholar 

  • Heppner K, Matrisian L, Jensen R and Rodgers W (1996) Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol 149: 273–282

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hewitt RE and Dano K (1996) Stromal cell expression of components of matrix degrading protease systems in human cancer. Enzyme Protein 49: 163–173

    Article  CAS  PubMed  Google Scholar 

  • Jonat C, Rahmsdort HJ, Park K, Cato ACB, Gebel S, Ponta H and Herrlich P (1990) Anti-tumor promotion and anti-inflammation: down-modulation of AP-I (Fos/Jun) activity by glycocorticoid hormone. Cell 62: 1189–1204

    Article  CAS  PubMed  Google Scholar 

  • Jones J, Glynn P and Walker R (1999) Expression of MMP-2 and MMP-9, their inhibitors and the activator MT1-MMP in primary breast carcinomas. J Pathol 189: 161–168

    Article  CAS  PubMed  Google Scholar 

  • Kaplan EL and Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481

    Article  Google Scholar 

  • Karameris A, Panagou P, Tsilalis T and Bouros D (1997) Association of expression of metalloproteinases and their inhibitors with the metastatic potential of squamous-cell lung carcinomas. A molecular and immunohistochemical study. Am J Respir Crit Care Med 156: 1930–1936

    Article  CAS  PubMed  Google Scholar 

  • Kute TE, Hushe MS and Phyme AC (1980) Improvements in steroid receptor assays including rapid computer analysis of data. Anal Biochem 103: 272–279

    Article  CAS  PubMed  Google Scholar 

  • Liotta LA and Stetler-Steverson G (1991) Tumor invasion and metastasis: An imbalance of positive and negative regulation. Cancer Res 51: 5054–5059

    Google Scholar 

  • Magklara A, Scorilas A, Stephan C, Kristiansen G, Hauptmann S, Jung K and Diamandis EP (2000) Down-regulation of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) in malignant vs non-malignant prostatic tissue. Urology 56: 527–532

    Article  CAS  PubMed  Google Scholar 

  • Mira E, Manes S, Lacalle RA, Marquer G and Mortinez C (1999) Insulin-like growth factor-1 triggered cell migration and invasion are mediated by matrix metalloproteinase-9. Endocrinology 140: 1657–1664

    Article  CAS  PubMed  Google Scholar 

  • Nelson A, Fingleton B, Rothenberg M and Matrisian L (2000) Matrix metalloproteinase: Biologic activity and clinical implications. J Clin Oncol 18: 1135–1149

    Article  CAS  PubMed  Google Scholar 

  • Nielsen BS, Timshel S, Kjeldsen L, Sehested Pyke C, Borregaard N and Dano K (1996a) 92 kDa type IV collagenase (MMP-9) is expressed in neutrophils and macrophages but not in malignant epithelial cells in human colon cancer. Int J Cancer 65: 57–62

    Article  CAS  PubMed  Google Scholar 

  • Nielsen BS, Sehesed M, Timshel S, Pyke C and Dano K (1996b) Messenger RNA for urokinase plasminogen activator (uPA) is expressed in myofibroblasts adjacent to cancer cells in human breast cancer. Lab Investigations 74: 168–177

    CAS  Google Scholar 

  • Nielsen BS, Sehested M, Kjeldsen L, Borregaard N, Rygaard J and Danon K (1997) Expression of matrix metalloprotease-9 in vascular pericytes in human breast cancer. Lab Investigation 77: 345–355

    CAS  Google Scholar 

  • Pacheco MM, Mourao M, Edson BM, Nishimoto IN and Brentani MM (1998) Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations. Clin Exp Metastasis 16: 577–585

    Article  CAS  PubMed  Google Scholar 

  • Ree AH, Bjørnland K, Brünner N, Johansen HT, Pedersen KB, Aasen AO and Fodstad O (1998) Regulation of tissue-degrading factors and in vitro invasiveness in progression of breast cancer cells. Clin Exp Metastasis 16: 205–215

    Article  CAS  PubMed  Google Scholar 

  • Remacle AG, Noël A, Duggan C, McDermott E, O'Higgins N, Foidart JM and Duffy MJ (1998) Assay of matrix metalloproteinases types 1,2,3 and 9 in breast cancer. Br J Cancer 77: 926–931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rha SY, Kim JH, Roh JK, Lee KS, Min JS, Kim BS and Chung HC (1997) Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression. Br Cancer Res Treatment 43: 175–181

    Article  CAS  Google Scholar 

  • Rha SY, Yang WI, Kim JH, Roh JK, Min JS, Lee KS, Kim BS and Chung HC (1998) Different expression patterns of MMP-2 and MMP-9 in breast cancer. Oncol Rep 5: 875–879

    CAS  PubMed  Google Scholar 

  • Salamonsen LA, Butt AR, Hammond R, Garcia S and Zhang J (1997) Production of endometrial matrix metalloproteinases, but not their tissue inhibitors are modulated by progesterone withdrawal in an in vitro model for menstruation. J Clin Endocrinol Metab 78: 1409–1415

    Google Scholar 

  • Scorilas A, Yotis J, Gouriotis D, Keramopoulos A, Ampela K, Trangas T and Talieri M (1993) Cathepsin-D and c-erbB-2 have an additive prognostic value for breast cancer patients. Anticancer Res 13: 1895–1900

    CAS  PubMed  Google Scholar 

  • Scorilas A, Yotis J, Stravolemos K, Gouriotis D, Keramopoulos A, Ampela K, Talieri M and Trangas T (1995) c-erB-2 overexpression may be used as an independent prognostic factor for breast cancer patients. Anticancer Res 15: 1543–1548

    CAS  PubMed  Google Scholar 

  • Scorilas A, Yotis J, Pateras CH, Trangas TH and Talieri M (1999a) Predictive value of c-erbB-2 and Cathepsin-D for Greek breast cancer patients using univariate and multivariate analysis. Clin Cancer Res 5: 815–821

    CAS  PubMed  Google Scholar 

  • Scorilas A, Trangas TH, Yotis J, Pateras CH and Talieri M (1999b) Determination of c-myc amplifications and overexpression in breast cancer patients. Evaluation of its prognostic value against c-erbB-2, cathepsin-D and clinicopathologic characteristics using univariate and multivariate analysis. Br J Cancer 81: 1385–1391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scorilas A, Diamandis E, Levesque M, Papanastasiou-Diamandis A, Khoszavi M, Giai M, Ponzone R, Roagua R, Sismondi P and López-Otin C (1999c) Immuno-enzymatically determined pepsinogen C concentration in breast tumor cytosols: An independent favorable prognostic factor in node-positive patients. Clin Cancer Res 5: 1778–1785

    CAS  PubMed  Google Scholar 

  • Scorilas A, Talieri M, Ardavanis A, Courtis N, Yotis J, Dimitriadis E, Tsiapalis C and Trangas T (2000a) Polyadenylate polymerase enzymatic activity in mammary tumor cytosols: A new independent prognostic marker in primary breast cancer. Cancer Res 60: 5427–5433

    CAS  PubMed  Google Scholar 

  • Scorilas A, Black M, Talieri M and Diamandis E (2000b) Genomic organization, physical mapping and expression analysis of the human protein arginine methyltransferase 1 gene. Biochem Biophys Res Commun 278: 349–359

    Article  CAS  PubMed  Google Scholar 

  • Spiessl B, Beahrs OH, Hermanek P, Hutter RVP, Scheibe O, Sobin LH and Wagner G (1989) Illustrated guide to the TNM/p TNM classification of malignant tumours. TNM Atlas, 3rd edn

  • Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA and Goldberg GI (1995) Mechanisms of cell surface activation of 72-kDa type IV collagenase. J Biol Chem 270: 1–8

    Article  Google Scholar 

  • Sugiura Y, Shimada H, Seeger R, Lang W and Declerck YA (1998) Matrix metalloproteinases-2 and -9 are expressed in human neuroblastoma: Contribution of stromal cells to their production and correlation with metastasis. Cancer Res 58: 2209–2216

    CAS  PubMed  Google Scholar 

  • Takeha S, Fujiyama Y, Bamda T, Sorsa T, Nagura H and Ohtani H (1997) Stromal expression of MMP-9 and urokinase receptor is inversely associated with liver metastasis and with infiltrating growth in human colorectal cancer: A novel approach from immune/inflammatory aspect. Jpn J Cancer 88: 72–81

    Article  CAS  Google Scholar 

  • Thorpe SM, Christensen IJ, Rasmussen BB and Rose C (1993) Short recurrence-free survival associated with high oestrogen receptor levels in the natural history of postmenopausal primary breast cancer. Eur J Cancer 29A: 971–977

    Article  CAS  PubMed  Google Scholar 

  • Tryggvason K, Hoyhtya M and Pyke C (1993) Type IV collagenase in invasive tumors. Br Cancer Res Treat 24: 209–218

    Article  CAS  Google Scholar 

  • Visscher DW, Hoyhtya M, Ottosen SK, Liang C-M, Sarkar FH, Crissman JD and Fridman R (1994) Enhanced expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the stroma of breast carcinomas correlates with tumor recurrence. Int J Cancer 59: 339–344

    Article  CAS  PubMed  Google Scholar 

  • Vizoso F, Sanchez LM, Diez-Itza I, Merino AM and Lopez-Otin C (1995) Pepsinogen C is a new prognostic marker in primary breast cancer. J Clin Oncol 13: 54–61

    Article  CAS  PubMed  Google Scholar 

  • Vu TH and Werb Z (1998) Gelatinase B Structure, regulation and function. In: Matrix metalloproteinases, Parks W C Mecham R P (eds) pp 115–148. Academic Press: San Diego, CA

    Chapter  Google Scholar 

  • Yan S, Sameni M and Sloane BF (1998) Cathepsin B and human tumor progression. Biol Chem 379: 113–123

    CAS  PubMed  Google Scholar 

  • Yousef GM, Scorilas A and Diamandis EP (2000) Genomic organization, mapping, tissue expression and hormonal regulation of trypsin-like serine protease (TLSP PRSS20), a new member of the human kallikrein gene family. Genomics 63: 88–96

    Article  CAS  PubMed  Google Scholar 

  • Yousef G, Scorilas A, Jung K, Aschworth L and Diamandis EP (2001) The new human kallikrein gene KLK15 is up-regulated in prostate cancer. J Biol Chem 276: 53–61

    Article  CAS  PubMed  Google Scholar 

  • Yu H, Levesque MA, Clark GM and Diamandis EP (1998) Prognostic value of prostate-specific antigen for women with breast cancer: a large United States cohort study. Clin Cancer Res 4: 1489–1497

    CAS  PubMed  Google Scholar 

  • Yu Q and Stamenkovic (1999) Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invation. Genes Dev 13: 35–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zucker S, Hymowitz M, Conner C, Zarrabi H, Hurewitz A, Matrisian L, Boyd D, Nicolson G and Montana S (1999) Measurement of matrix metalloproteinases and tissue inhibitors of metalloproteinases in blood and tissues. Ann NY Acad Sci 878: 212–227

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes
  1. A Scorilas

    Present address: National Center of Scientific Research ‘Demokritos’, IPC, Athens, 15310, Greece

Authors and Affiliations

  1. ‘G.Papanikolaou’ Research Center of Oncology, ‘St. Savas’ Hospital, 171 Alexandras Avenue, Athens, 11522, Greece

    A Scorilas, T Trangas & M Talieri

  2. Department of Pathology, ‘St. Savas’ Hospital, 171 Alexandras Avenue, Athens, 11522, Greece

    N Arnogiannaki

  3. Department of Oncology, ‘St. Savas’ Hospital, 171 Alexandras Avenue, Athens, 11522, Greece

    A Ardavanis

  4. Department of Surgery, ‘St. Savas’ Hospital, 171 Alexandras Avenue, Athens, 11522, Greece

    P Bassilopoulos

  5. Department of Pathology, 401 Army General Hospital, Athens, Greece

    A Scorilas & A Karameris

Authors
  1. A Scorilas
    View author publications

    Search author on:PubMed Google Scholar

  2. A Karameris
    View author publications

    Search author on:PubMed Google Scholar

  3. N Arnogiannaki
    View author publications

    Search author on:PubMed Google Scholar

  4. A Ardavanis
    View author publications

    Search author on:PubMed Google Scholar

  5. P Bassilopoulos
    View author publications

    Search author on:PubMed Google Scholar

  6. T Trangas
    View author publications

    Search author on:PubMed Google Scholar

  7. M Talieri
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and permissions

About this article

Cite this article

Scorilas, A., Karameris, A., Arnogiannaki, N. et al. Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients. Br J Cancer 84, 1488–1496 (2001). https://doi.org/10.1054/bjoc.2001.1810

Download citation

  • Received: 15 June 2000

  • Revised: 22 February 2001

  • Accepted: 28 February 2001

  • Published: 29 May 2001

  • Issue date: 01 June 2001

  • DOI: https://doi.org/10.1054/bjoc.2001.1810

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • MMP-9
  • breast cancer
  • prognostic factor

This article is cited by

  • Quantifiable peptide library bridges the gap for proteomics based biomarker discovery and validation on breast cancer

    • Sung-Soo Kim
    • HyeonSeok Shin
    • Dong-Young Noh

    Scientific Reports (2023)

  • A Phage Display Derived Cyclized Peptide Inhibits Fibrosarcoma Cells Invasion via Suppression of MMP-9 Activity

    • Alireza Shoari
    • Saeed Khalili
    • Dennis W. P. M. Löwik

    International Journal of Peptide Research and Therapeutics (2022)

  • Prognostic values of tumoral MMP2 and MMP9 overexpression in breast cancer: a systematic review and meta-analysis

    • Hanfang Jiang
    • Huiping Li

    BMC Cancer (2021)

  • Euphorbia humifusa Willd exerts inhibition of breast cancer cell invasion and metastasis through inhibition of TNFα-induced MMP-9 expression

    • Soon Young Shin
    • Chang Gun Kim
    • Young Han Lee

    BMC Complementary and Alternative Medicine (2016)

  • Association of Fascin and matrix metalloproteinase-9 expression with poor prognostic parameters in breast carcinoma of Egyptian women

    • Nermeen Salah Youssef
    • Sarah Adel Hakim

    Diagnostic Pathology (2014)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open access publishing
  • About the Editors
  • Contact
  • Special Issues
  • For Advertisers
  • Subscribe

Publish with us

  • For Authors & Referees
  • Language editing services
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

British Journal of Cancer (Br J Cancer)

ISSN 1532-1827 (online)

ISSN 0007-0920 (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2025 Springer Nature Limited