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
Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours
Download PDF
Download PDF
  • Regular Article
  • Open access
  • Published: 11 September 2001

Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours

  • C Scotton1,
  • D Milliken2,
  • J Wilson1,
  • S Raju2 &
  • …
  • F Balkwill1 

British Journal of Cancer volume 85, pages 891–897 (2001)Cite this article

  • 1625 Accesses

  • 79 Citations

  • 9 Altmetric

  • Metrics details

This article has been updated

Abstract

To understand the chemokine network in a tissue, both chemokine and chemokine receptor expression should be studied. Human epithelial ovarian tumours express a range of chemokines but little is known about the expression and localisation of chemokine receptors. With the aim of understanding chemokine action in this cancer, we investigated receptors for CC–chemokines and their ligands in 25 biopsies of human ovarian cancer. CC–chemokine receptor mRNA was generally absent from solid tumours, the exception being CCR1 which was detected in samples from 75% of patients. CCR1 mRNA localised to macrophages and lymphocytes and there was a correlation between numbers of CD8+ and CCR1 expressing cells (P = 0.031). mRNA for 6 CC-chemokines was expressed in a majority of tumour samples. In a monocytic cell line in vitro, we found that CCR1 mRNA expression was increased 5-fold by hypoxia. We suggest that the CC-chemokine network in ovarian cancer is controlled at the level of CC-chemokine receptors and this may account for the phenotypes of infiltrating cells found in these tumours. The leukocyte infiltrate may contribute to tumour growth and spread by providing growth survival factors and matrix metalloproteases. Thus, CCR1 may be a novel therapeutic target in ovarian cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

Similar content being viewed by others

Macrophage-derived CCL23 upregulates expression of T-cell exhaustion markers in ovarian cancer

Article 24 June 2022

Integrated immuno-transcriptomic analysis of ovarian cancer identifies a four-chemokine-dominated subtype with antitumor immune-active phenotype and favorable prognosis

Article 02 August 2024

CXCL9 inhibits tumour growth and drives anti-PD-L1 therapy in ovarian cancer

Article Open access 21 March 2022

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

  • Altman DG (1991). Practical statistics for medical research. Chapman and Hall: London

    Google Scholar 

  • Baggiolini M and Moser B (1997) Blocking chemokine receptors. J Exp Med 186: 1189–1191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonecchi R, Polentarutti N, Luini W, Borsatti A, Bernasconi S, Locati M, Power C, Proudfoot A, Wells TNC, Mackay C, Mantovani A and Sozzani S (1999) Up-regulation of CCR1 and CCR3 and induction of chemotaxis to CC chemokines by IFN-gamma in human neutrophils. J Immunol 162: 474–479

    CAS  PubMed  Google Scholar 

  • Bottazzi B, Ghezzi P, Taraboletti G, Salmona M, Colombo N, Bonazzi C, Mangioni C and Mantovani A (1985) Tumor-derived chemotactic factor(s) from human ovarian carcinoma: evidence for a role in the regulation of macrophage content of neoplastic tissues. Int J Cancer 36: 167–173

    Article  CAS  PubMed  Google Scholar 

  • Burke F, Relf M, Negus R and Balkwill F (1996) A cytokine profile of normal and malignant ovary. Cytokine 8: 578–585

    Article  CAS  PubMed  Google Scholar 

  • Car BD, Meloni F, Luisetti M, Semenzato G, Gialdroni-Grassi G and Walz A (1994) Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med 149: 655–659

    Article  CAS  PubMed  Google Scholar 

  • Clore GM and Gronenborn AM (1995) Three-dimensional structures of alpha and beta chemokines. Faseb J 9: 57–62

    Article  CAS  PubMed  Google Scholar 

  • Colantonio L, Iellem A, Clissi B, Pardi R, Rogge L, Sinigaglia F and Dambrosio D (1999) Upregulation of integrin alpha 6/beta 1 and chemokine receptor CCR1 by interleukin-12 promotes the migration of human type 1 helper T cells. Blood 94: 2981–2989

    CAS  PubMed  Google Scholar 

  • Ebnet K and Vestweber D (1999) Molecular mechanisms that control leukocyte extravasation: the selectins and the chemokines. Histochem Cell Biol 112: 1–23

    Article  CAS  PubMed  Google Scholar 

  • Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD and Semenza GL (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol-Cell-Biol 16: 4604–4613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao JL, Wynn TA, Chang Y, Lee EJ, Broxmeyer HE, Cooper S, Tiffany HL, Westphal H, Kwon-Chung J and Murphy PM (1997) Impaired host defense, hematopoiesis, granulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1. J Exp Med 185: 1959–1968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao W, Topham PS, King JA, Smiley ST, Csizmadia V, Lu B, Gerard CJ and Hancock WW (2000) Targeting of the chemokine receptor CCR1 suppresses development of acute and chronic cardiac allograft rejection. J Clin Invest 105: 35–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Griffiths L, Binley K, Iqball S, Kan O, Maxwell P, Ratcliffe P, Lewis C, Harris A, Kingsman S and Naylor S (2000) The macrophage-a novel system to deliver gene therapy to pathological hypoxia. Gene Ther 7: 255–262

    Article  CAS  PubMed  Google Scholar 

  • Grimshaw MJ and Balkwill FR (2001) Inhibition of monocyte and macrophage chemotaxis by hypoxia and inflammation-a potential mechanism. Eur J Immunol 31: 480–489

    Article  CAS  PubMed  Google Scholar 

  • Grutkoski PS, Graeber CT, Damico R, Keeping H and Simms HH (1999) Regulation of IL-8RA (CXCR1) expression in polymorphonuclear leukocytes by hypoxia/reoxygenation. J Leukoc Biol 65: 171–178

    Article  CAS  PubMed  Google Scholar 

  • Hockel M, Schlenger K, Hockel S, Aral B, Schaffer U and Vaupel P (1998) Tumor hypoxia in pelvic recurrences of cervical cancer. Int J Cancer 79: 365–369

    Article  CAS  PubMed  Google Scholar 

  • Hosaka S, Akahoshi T, Wada C and Kondo H (1994) Expression of the chemokine superfamily in rheumatoid arthritis. Clin Exp Immunol 97: 451–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Howard OMZ, Oppenheim JJ and Wang JM (1999) Chemokines as molecular targets for therapeutic intervention. J Clin Immunol 19: 280–292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurihara T, Warr G, Loy J and Bravo R (1997) Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J Exp Med 186: 1757–1762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu B, Rutledge BJ, Gu L Fiorillo J, Lukacs NW, Kunkel SL, North R, Gerard C and Rollins BJ (1998) Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J Exp Med 187: 601–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mantovani A (1994) Tumor-associated macrophages in neoplastic progression: a paradigm for the in vivo function of chemokines. Lab Invest 71: 5–16

    CAS  PubMed  Google Scholar 

  • Mantovani A, Bottazzi B, Colotta F, Sozzani S and Ruco L (1992) The origin and function of tumor-associated macrophages. Immunol Today 13: 265–270

    Article  CAS  PubMed  Google Scholar 

  • Mantovani A, Allavena P, Vecchi A and Sozzani S (1998) Chemokines and chemokine receptors during activation and deactivation of monocytes and dendritic cells and in amplification of th1 versus th2 responses. Int J Clin Lab Res 28: 77–82

    Article  CAS  PubMed  Google Scholar 

  • Mattei S, Colombo MP, Melani C, Silvani A, Parmiani G and Herlyn M (1994) Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. Int J Cancer 56: 853–857

    Article  CAS  PubMed  Google Scholar 

  • Maxwell P and Ratcliffe P (1998) Regulation of expression of the erythropoietin gene. Curr Opin Hematol 5: 166–170

    Article  CAS  PubMed  Google Scholar 

  • Naylor MS, Stamp GW and Balkwill FR (1990) Investigation of cytokine gene expression in human colorectal cancer. Cancer Res 50: 4436–4440

    CAS  PubMed  Google Scholar 

  • Naylor MS, Stamp GW, Foulkes WD, Eccles D and Balkwill FR (1993) Tumor necrosis factor and its receptors in human ovarian cancer. Potential role in disease progression. J Clin Invest 91: 2194–2206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Negus RP, Stamp GW, Relf MG, Burke F, Malik ST, Bernasconi S, Allavena P, Sozzani S, Mantovani A and Balkwill FR (1995) The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer. Journal of Clinical Investigation 95: 2391–2396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Negus RP, Stamp GW, Hadley J and Balkwill FR (1997) Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am J Pathol 150: 1723–1734

    CAS  PubMed  PubMed Central  Google Scholar 

  • Negus RP, Turner L, Burke F and Balkwill FR (1998) Hypoxia down-regulates MCP-1 expression: implications for macrophage distribution in tumors. J Leukoc Biol 63: 758–765

    Article  CAS  PubMed  Google Scholar 

  • Quandt K, Frech K, Karas H, Wingender E and Werner T (1995) Matlnd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. Nucleic Acids Res 23: 4878–4884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schweickart VL, Epp A, Raport CJ and Gray PW (2000) CCR11 is a functional receptor for the monocyte chemoattractant protein family of chemokines. J Biol Chem 275: 9550–9556

    Article  CAS  PubMed  Google Scholar 

  • Sica A, Saccani A, Borsatti A, Power CA, Wells TN, Luini W, Polentarutti N, Sozzani S and Mantovani A (1997) Bacterial lipopolysaccharide rapidly inhibits expression of C-C chemokine receptors in human monocytes. Journal of Experimental Medicine 185: 969–974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sica A, Saccani A, Bottazzi B, Bernasconi S, Allavena P, Gaetano B, Fei F, LaRosa G, Scotton C, Balkwill F and Mantovani A (2000) Defective Expression of the Monocyte Chemotactic Protein-1 Receptor CCR2 in Macrophages Associated with Human Ovarian Carcinoma. J Immunol 164: 733–738

    Article  CAS  PubMed  Google Scholar 

  • Signoret N, Rosenkilde MM, Klasse PJ, Schwartz TW, Malim MH, Hoxie JA and Marsh M (1998) Differential regulation of cxcr4 and ccr5 endocytosis. J Cell Sci 111: 2819–2830

    CAS  PubMed  Google Scholar 

  • Takeya M, Yoshimura T, Leonard EJ and Takahashi K (1993) Detection of monocyte chemoattractant protein-1 in human atherosclerotic lesions by an anti-monocyte chemoattractant protein-1 monoclonal antibody. Hum Pathol 24: 534–539

    Article  CAS  PubMed  Google Scholar 

  • Turner L, Scotton C, Negus R and Balkwill F (1999) Hypoxia inhibits macrophage migration. Eur J Immunol 29: 2280–2287

    Article  CAS  PubMed  Google Scholar 

  • Turner SJ, Domin J, Waterfield MD, Ward SG and Westwick J (1998) The CC chemokine monocyte chemotactic peptide-1 activates both the class I p85/p110 phosphatidylinositol 3-kinase and the class II P13K-C2alpha. J Biol Chem 273: 25987–25995

    Article  CAS  PubMed  Google Scholar 

  • Van Coillie E, Froyen G, Nomiyama H, Miura R, Fiten P, Van Aelst I, Van Damme J and Opdenakker G (1997) Human monocyte chemotactic protein-2: cDNA cloning and regulated expression of mRNA in mesenchymal cells. Biochem Biophys Res Commun 231: 726–730

    Article  CAS  PubMed  Google Scholar 

  • Vaupel P, Thews O, Kelleher DK and Hoeckel M (1998) Current status of knowledge and critical issues in tumor oxygenation. Results from 25 years research in tumor pathophysiology. Adv Exp Med Biol 454: 591–602

    Article  CAS  PubMed  Google Scholar 

  • Wang JM, Deng XY, Gong WH and Su SB (1998) Chemokines and their role in tumor-growth and metastasis. J Immunol Methods 220: 1–17

    Article  CAS  PubMed  Google Scholar 

  • Xu L, Xie K, Mukaida N, Matsushima K and Fidler IJ (1999) Hypoxia-induced elevation in interleukin-8 expression by human ovarian carcinoma cells. Cancer Res 59: 5822–5829

    CAS  PubMed  Google Scholar 

  • Yoong KF, Afford SC, Jones R, Aujla P, Qin S, Price K, Hubscher SG and Adams DH (1999) Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma. Hepatology 30: 100–111

    Article  CAS  PubMed  Google Scholar 

  • Zella D, Barabitskaja O, Casareto L, Romerio F, Secchiero P, Reitz MS, Gallo RC and Weichold FF (1999) Recombinant IFN-alpha (2b) increases the expression of apoptosis receptor CD95 and chemokine receptors CCR1 and CCR3 in monocytoid cells. J Immunol 163: 3169–3175

    CAS  PubMed  Google Scholar 

  • Zlotnik A and Yoshie O (2000) Chemokines: A new classification system and their role in immunity. Immunity 12: 121–127

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. ICRF Translational Oncology Laboratory, St Bartholomew’s and Royal London School of Medicine and Dentistry, Science Building, Charterhouse Square, London, EC1M 6BQ, UK

    C Scotton, J Wilson & F Balkwill

  2. Department of Obstetrics and Gynaecology, Guy’s and St Thomas’ Hospital Trust, Lambeth Palace Road, London, SE1 7EH, UK

    D Milliken & S Raju

Authors
  1. C Scotton
    View author publications

    Search author on:PubMed Google Scholar

  2. D Milliken
    View author publications

    Search author on:PubMed Google Scholar

  3. J Wilson
    View author publications

    Search author on:PubMed Google Scholar

  4. S Raju
    View author publications

    Search author on:PubMed Google Scholar

  5. F Balkwill
    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

Scotton, C., Milliken, D., Wilson, J. et al. Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours. Br J Cancer 85, 891–897 (2001). https://doi.org/10.1054/bjoc.2001.2020

Download citation

  • Received: 19 March 2001

  • Revised: 06 June 2001

  • Accepted: 11 June 2001

  • Published: 11 September 2001

  • Issue date: 14 September 2001

  • DOI: https://doi.org/10.1054/bjoc.2001.2020

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

  • chemokine
  • ovarian cancer
  • CCR1
  • hypoxia

This article is cited by

  • Evolving notions on immune response in colorectal cancer and their implications for biomarker development

    • Fabio Grizzi
    • Gianluca Basso
    • Luigi Laghi

    Inflammation Research (2018)

  • Pre-operative neutrophil count and neutrophil-lymphocyte count ratio (NLCR) in predicting the histological grade of paediatric brain tumours: a preliminary study

    • J. R. F. Wilson
    • F. Saeed
    • P. D. Chumas

    Acta Neurochirurgica (2018)

  • CCL15/CCR1 axis is involved in hepatocellular carcinoma cells migration and invasion

    • Yueguo Li
    • Jing Wu
    • Peng Zhang

    Tumor Biology (2016)

  • Cancer-Related Inflammation

    • Juliana Candido
    • Thorsten Hagemann

    Journal of Clinical Immunology (2013)

  • Role of Bone Marrow-Derived Cells in Angiogenesis: Focus on Macrophages and Pericytes

    • Yanping Ding
    • Nan Song
    • Yongzhang Luo

    Cancer Microenvironment (2012)

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