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
  • 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
Quantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer
Download PDF
Your article has downloaded

Similar articles being viewed by others

Slider with three articles shown per slide. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide.

A straightforward method to quantify circulating mRNAs as biomarkers of colorectal cancer

15 February 2023

Marie Grosgeorges, Laurence Picque Lasorsa, … Philippe Blache

Analytical performance of a new automated chemiluminescent magnetic immunoassays for soluble PD-1, PD-L1, and CTLA-4 in human plasma

12 July 2019

Megumi Goto, Kenji Chamoto, … Tasuku Honjo

The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer

19 February 2019

Malgorzata Banys-Paluchowski, Isabell Witzel, … Volkmar Müller

Stability and reproducibility of proteomic profiles measured with an aptamer-based platform

30 May 2018

Claire H. Kim, Shelley S. Tworoger, … A. Heather Eliassen

Total circulating microRNA level as an independent prognostic marker for risk stratification in breast cancer

22 March 2022

Aoife Ward Gahlawat, Lavinia Fahed, … Sarah Schott

Circulating tumour DNA — looking beyond the blood

01 August 2022

Ann Tivey, Matt Church, … Natalie Cook

An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma

28 June 2021

Jongmin Park, Jun Seok Park, … Hakho Lee

Multiplex quantification of C-terminal alpha-1-antitrypsin peptides provides a novel approach for characterizing systemic inflammation

09 March 2022

Arite Bigalke, Christoph Sponholz, … Michael Kiehntopf

A Targeted Mass Spectrometric Assay for Reliable Sensitive Hepcidin Quantification

13 May 2019

Ahmed Moghieb, Lia Tesfay, … Charles Ansong

Download PDF
  • Open Access
  • Published: 09 April 1999

Quantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer

  • M N Holten-Andersen1,
  • G Murphy2,
  • H J Nielsen4,
  • A N Pedersen1,3,
  • I J Christensen1,
  • G Høyer-Hansen1,
  • N Brünner1 &
  • …
  • R W Stephens1 

British Journal of Cancer volume 80, pages 495–503 (1999)Cite this article

  • 1243 Accesses

  • 125 Citations

  • 6 Altmetric

  • Metrics details

This article has been updated

Summary

A kinetic enzyme-linked immunosorbent assay (ELISA) for plasma tissue inhibitor of metalloproteinase (TIMP)-1 was developed in order to examine the potential diagnostic and prognostic value of TIMP-1 measurements in cancer patients. The ELISA enabled specific detection of total TIMP-1 in EDTA, citrate and heparin plasma. The assay was rigorously tested and requirements of sensitivity, specificity, stability and good recovery were fulfilled. TIMP-1 levels measured in citrate plasma (mean 69.2 ± 13.1 μg l–1) correlated with TIMP-1 measured in EDTA plasma (mean 73.5 ± 14.2 μg l–1) from the same individuals in a set of 100 healthy blood donors (Spearman’s rho = 0.62, P < 0.0001). The mean level of TIMP-1 in EDTA plasma from 143 patients with Dukes’ stage D colorectal cancer was 240 ± 145 μg l–1 and a Mann–Whitney test demonstrated a highly significant difference between TIMP-1 levels in healthy blood donors and colorectal cancer patients (P < 0.0001). Similar findings were obtained for 19 patients with advanced breast cancer (mean 292 ± 331 μg l–1). The results show that TIMP-1 is readily measured in plasma samples by ELISA and that increased levels of TIMP-1 are found in patients with advanced cancer. It is proposed that plasma measurements of TIMP-1 may have value in the management of cancer patients.

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

  • Baker, T., Tickle, S., Wasan, H., Docherty, A., Isenberg, D. & Waxman, J. (1994). Serum metalloproteinases and their inhibitors: markers for malignant potential. Br J Cancer 70: 506–512.

    Article  CAS  Google Scholar 

  • Birkedal-Hansen, H., Moore, W. G., Bodden, M. K., Windsor, L. J., Birkedal-Hansen, B., DeCarlo, A. & Engler, J. A. (1993). Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4: 197–250.

    Article  CAS  Google Scholar 

  • Clark, I. M., Powell, L. K., Wright, J. K. & Cawston, the (1991). Polyclonal and monoclonal antibodies against human tissue inhibitor of metalloproteinases (TIMP) and the design of an enzyme-linked immunosorbent assay to measure TIMP. Matrix 11: 76–85.

    Article  CAS  Google Scholar 

  • Cooksley, S., Hipkiss, J. B., Tickle, S. P., Holmes, I. E., Docherty, A. J., Murphy, G. & Lawson, A. D. (1990). Immunoassays for the detection of human collagenase, stromelysin, tissue inhibitor of metalloproteinases (TIMP) and enzyme-inhibitor complexes. Matrix 10: 285–291.

    Article  CAS  Google Scholar 

  • Cooper, T. W., Eisen, A. Z., Stricklin, G. P. & Welgus, H. G. (1985). Platelet-derived collagenase inhibitor: characterization and subcellular localization. Proc Natl Acad Sci USA 82: 2779–2783.

    Article  CAS  Google Scholar 

  • De Nictolis, M., Garbisa, S., Lucarini, G., Goteri, G., Masiero, L., Ciavattini, A., Garzetti, G. G., Stetler-Stevenson, W. G., Fabris, G., Biagini, G. & Prat, J. (1996). 72-kilodalton type IV collagenase, type IV collagen, and Ki 67 antigen in serous tumors or the ovary: a clinicopathologic, immunohistochemical, and serological study. Int J Gynecol Pathol 15: 102–109.

    Article  CAS  Google Scholar 

  • DeClerck, Y. A., Perez, N., Shimada, H., Boone, T. C., Langley, K. E. & Taylor, S. M. (1992). Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res 52: 701–708.

    CAS  PubMed  Google Scholar 

  • Deng, G., Curriden, S. A., Wang, S., Rosenberg, S. & Loskutoff, D. J. (1996). Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? J Cell Biol 134: 1563–1571.

    Article  CAS  Google Scholar 

  • Fong, K. M. (1996). TIMP1 and adverse prognosis in non-small cell lung cancer. Clin Cancer Res 2: 1369–1372.

    CAS  PubMed  Google Scholar 

  • Frandsen, T. L., Stephens, R. W., Pedersen, A. N., Engelholm, L. H., Holst-Hansen, C. & Brünner, N. (1998). Plasminogen activator inhibitor type 1 (PAI-1) in cancer: a potential new target for antiinvasive and antimetastatic therapy. Drugs of the Future 23: 873–883.

    Article  CAS  Google Scholar 

  • Fujimoto, N., Zhang, J., Iwata, K., Shinya, T., Okada, Y. & Hayakawa, T. (1993). A one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases-2 using monoclonal antibodies. Clin Chim Acta 220: 31–45.

    Article  CAS  Google Scholar 

  • Fung, K., Nowak, L., Lein, M., Henke, W., Schnorr, D. & Loening, S. A. (1996). Role of specimen collection in preanalytical variation of metalloproteinases and their inhibitors in blood. Clin Chem 42: 2043–2045.

    Google Scholar 

  • Gohji, K., Fujimoto, N., Fujii, A., Komiyama, T., Okawa, J. & Nakajima, M. (1996). Prognostic significance of circulating matrix metalloproteinase-2 to tissue inhibitor of metalloproteinases-2 ratio in recurrence of urothelial cancer after complete resection. Cancer Res 56: 3196–3198.

    CAS  PubMed  Google Scholar 

  • Goldberg, G. I., Strongin, A., Collier, I. E., Genrich, L. T. & Marmer, B. L. (1992). Interaction of 92-kDa type IV collagenase with the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin. J Biol Chem 267: 4583–4591.

    CAS  PubMed  Google Scholar 

  • Hayakawa, T., Yamashita, K., Tanzawa, K., Uchijima, E. & Iwata, K. (1992). Growth-promoting activity of tissue inhibitor of metalloproteinases-1 (TIMP-1) for a wide range of cells. A possible new growth factor in serum. FEBS Lett 298: 29–32.

    Article  CAS  Google Scholar 

  • Hembry, R. M., Murphy, G. & Reynolds, J. J. (1985). Immunolocalization of tissue inhibitor of metalloproteinases (TIMP) in human cells. Characterization and use of a specific antiserum. J Cell Sci 73: 105–119.

    CAS  PubMed  Google Scholar 

  • Jung, K., Nowak, L., Lein, M., Henke, W., Schnorr, D. & Loening, S. A. (1996). What kind of specimen should be selected for determining tissue inhibitor of metalloproteinase-1 (TIMP-1) in blood? Clin Chim Acta 254: 97–100.

    Article  CAS  Google Scholar 

  • Kawano, N., Osawa, H., Ito, T., Nagashima, Y., Hirahara, F., Inayama, Y., Nakatani, Y., Kimura, S., Kitajima, H., Koshikawa, N., Miyazaki, K. & Kitamura, H. (1997). Expression of gelatinase A, tissue inhibitor of metalloproteinases-2, matrilysin, and trypsin(ogen) in lung neoplasms: an immunohistochemical study. Hum Pathol 28: 613–622.

    Article  CAS  Google Scholar 

  • Khokha, R. & Waterhouse, P. (1993). The role of tissue inhibitor of metalloproteinase-1 in specific aspects of cancer progression and reproduction. J Neurooncol 18: 123–127.

    Article  Google Scholar 

  • Khokha, R., Zimmer, M. J., Graham, C. H., Lala, P. K. & Waterhouse, P. (1992a). Suppression of invasion by inducible expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in B16-F10 melanoma cells. J Natl Cancer Inst 84: 1017–1022.

    Article  CAS  Google Scholar 

  • Khokha, R., Zimmer, M. J., Wilson, S. M. & Chambers, A. F. (1992b). Up-regulation of TIMP-1 expression in B16-F10 melanoma cells suppresses their metastatic ability in chick embryo. Clin Exp Metastasis 10: 365–370.

    Article  CAS  Google Scholar 

  • Kleiner, Jr D. E., Tuuttila, A., Tryggvason, K. & Stetler-Stevenson, W. G. (1993). Stability analysis of latent and active 72-kDa type IV collagenase: the role of tissue inhibitor of metalloproteinases-2 (TIMP-2). Biochemistry 32: 1583–1592.

    Article  CAS  Google Scholar 

  • Kodama, S., Yamashita, K., Kishi, J., Iwata, K. & Hayakawa, T. (1989). A sandwich enzyme immunoassay for collagenase inhibitor using monoclonal antibodies. Matrix 9: 1–6.

    Article  CAS  Google Scholar 

  • Liotta, L. A., Steeg, P. S. & Stetler-Stevenson, W. G. (1991). Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64: 327–336.

    Article  CAS  Google Scholar 

  • MacDougall, J. R. & Matrisian, L. M. (1995). Contributions of tumor and stromal matrix metalloproteinases to tumor progression, invasion and metastasis. Cancer Metastasis Rev 14: 351–362.

    Article  CAS  Google Scholar 

  • Matrisian, L. M. (1992). The matrix-degrading metalloproteinases. Bioessays 14: 455–463.

    Article  CAS  Google Scholar 

  • Mimori, K., Mori, M., Shiraishi, T., Fujie, T., Baba, K., Haraguchi, M., Abe, R., Ueo, H. & Akiyoshi, T. (1997). Clinical significance of tissue inhibitor of metalloproteinase expression in gastric carcinoma. Br J Cancer 76: 531–536.

    Article  CAS  Google Scholar 

  • Moll, U. M., Youngleib, G. L., Rosinski, K. B. & Quigley, J. P. (1990). Tumor promoter-stimulated Mr 92,000 gelatinase secreted by normal and malignant human cells: isolation and characterization of the enzyme from HT1080 tumor cells. Cancer Res 50: 6162–6170.

    CAS  PubMed  Google Scholar 

  • Moutsiakis, D., Mancuso, P., Krutzsch, H., Stetler-Stevenson, W. G. & Zucker, S. (1992). Characterization of metalloproteinases and tissue inhibitors of metalloproteinases in human plasma. Connect Tissue Res 28: 213–230.

    Article  CAS  Google Scholar 

  • Murphy, G., Houbrechts, A., Cockett, M. I., Williamson, R. A., O’Shea, M. & Docherty, A. J. (1991). The N-terminal domain of tissue inhibitor of metalloproteinases retains metalloproteinase inhibitory activity. Biochemistry 30: 8097–8102.

    Article  CAS  Google Scholar 

  • Nuovo, G. J., MacConnell, P. B., Simsir, A., Valea, F. & French, D. L. (1995). Correlation of the in situ detection of polymerase chain reaction-amplified metalloproteinase complementary DNAs and their inhibitors with prognosis in cervical carcinoma. Cancer Res 55: 267–275.

    CAS  PubMed  Google Scholar 

  • Stetler-Stevenson, W. G., Krutzsch, H. C. & Liotta, L. A. (1989). Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family. J Biol Chem 264: 17374–17378.

    CAS  PubMed  Google Scholar 

  • Stetler-Stevenson, W. G., Liotta, L. A. & Kleiner, Jr D. E. (1993). Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis. FASEB J 7: 1434–1441.

    Article  CAS  Google Scholar 

  • Stetler-Stevenson, W. G., Hewitt, R. & Corcoran, M. (1996). Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic. Semin Cancer Biol 7: 147–154.

    Article  CAS  Google Scholar 

  • Thorgeirsson, U. P., Lindsay, C. K., Cottam, D. W. & Gomez, D. E. (1993). Tumor invasion, proteolysis, and angiogenesis. J Neurooncol 18: 89–103.

    Article  Google Scholar 

  • Welgus, H. G., Jeffrey, J. J., Eisen, A. Z., Roswit, W. T. & Stricklin, G. P. (1985). Human skin fibroblast collagenase: interaction with substrate and inhibitor. Coll Relat Res 5: 167–179.

    Article  CAS  Google Scholar 

  • Wilhelm, S. M., Collier, I. E., Marmer, B. L., Eisen, A. Z., Grant, G. A. & Goldberg, G. I. (1989). SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem 264: 17213–17221.

    CAS  PubMed  Google Scholar 

  • Yoshiji, H., Gomez, D. E. & Thorgeirsson, U. P. (1996). Enhanced RNA expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in human breast cancer. Int J Cancer 69: 131–134.

    Article  CAS  Google Scholar 

  • Zucker, S., Lysik, R. M., DiMassimo, B. I., Zarrabi, H. M., Moll, U. M., Grimson, R., Tickle, S. P. & Docherty, A. J. (1995). Plasma assay of gelatinase B: tissue inhibitor of metalloproteinase complexes in cancer. Cancer 76: 700–708.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Finsen Laboratory, Copenhagen University Hospital, Strandboulevarden 49, Copenhagen, 2100, Denmark

    M N Holten-Andersen, A N Pedersen, I J Christensen, G Høyer-Hansen, N Brünner & R W Stephens

  2. Strangeways Laboratories, Cambridge University, Cambridge, UK

    G Murphy

  3. Department of Oncology, Herlev Hospital, Herlev Ringvej, Herlev, 2730, Denmark

    A N Pedersen

  4. Department of Gastroenterology, Hvidovre Hospital, Kettegårds Alle, Hvidovre, 2650, Denmark

    H J Nielsen

Authors
  1. M N Holten-Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H J Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A N Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I J Christensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Høyer-Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N Brünner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R W Stephens
    View author publications

    You can also search for this author in 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

Holten-Andersen, M., Murphy, G., Nielsen, H. et al. Quantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer. Br J Cancer 80, 495–503 (1999). https://doi.org/10.1038/sj.bjc.6690384

Download citation

  • Received: 16 June 1998

  • Revised: 28 September 1998

  • Accepted: 22 October 1998

  • Published: 09 April 1999

  • Issue Date: 01 May 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690384

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

  • TIMP-1
  • ELISA
  • plasma
  • cancer
  • blood donors

This article is cited by

  • Overexpression of TIMP-1 and Sensitivity to Topoisomerase Inhibitors in Glioblastoma Cell Lines

    • Charlotte Aaberg-Jessen
    • Louise Fogh
    • Bjarne Winther Kristensen

    Pathology & Oncology Research (2019)

  • Comparative studies of TIMP-1 immunohistochemistry, TIMP-1 FISH analysis and plasma TIMP-1 in glioblastoma patients

    • Charlotte Aaberg-Jessen
    • Bo Halle
    • Bjarne W. Kristensen

    Journal of Neuro-Oncology (2016)

  • Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study

    • Robert Linder
    • Eva Rönmark
    • Anne Lindberg

    Respiratory Research (2015)

  • TIMP-1 and CEA as biomarkers in third-line treatment with irinotecan and cetuximab for metastatic colorectal cancer

    • Karen-Lise Garm Spindler
    • Ib Jarle Christensen
    • Nils Brünner

    Tumor Biology (2015)

  • Detection of serological biomarkers by proximity extension assay for detection of colorectal neoplasias in symptomatic individuals

    • Stine Buch Thorsen
    • Martin Lundberg
    • Erika Assarsson

    Journal of Translational Medicine (2013)

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
  • 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
  • Nano
  • Protocol Exchange
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

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

Libraries & institutions

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

Advertising & partnerships

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

Career development

  • Nature Careers
  • Nature Conferences
  • Nature events

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Italy
  • Nature Japan
  • Nature Korea
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • California Privacy Statement
Springer Nature

© 2023 Springer Nature Limited