Invasion and Metastasis

Original Paper

Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases in Non-Small-Cell Lung Cancer

Suzuki M.a · Iizasa T.a · Fujisawa T.a · Baba M.a · Yamaguchi Y.a · Kimura H.b · Suzuki H.a

Author affiliations

aDepartment of Surgery, Institute of Pulmonary Cancer Research, Chiba University School of Medicine, and bDivision of Thoracic Disease, Chiba Cancer Center, Chiba, Japan

Keywords: Matrix metalloproteinaseTissue inhibitor of metalloproteinaseLung cancer

Related Articles for ""
Invasion Metastasis 1998/99;18:134–141
https://doi.org/10.1159/000024506

Log in to MyKarger to check if you already have access to this content.




Forgot your password
Sign up to MyKarger

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more
CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!


If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

For eJournal Archive and eJournal Backfiles information please contact Karger service

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: August 25, 1999
Issue release date: August 1999

Number of Print Pages: 8
Number of Figures: 5
Number of Tables: 1

ISSN: 0251-1789 (Print)
eISSN: 1423-0119 (Online)

For additional information: https://www.karger.com/IAM

Abstract

Expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 was studied in non-small-cell lung cancer (NSCLC). Activity of MMP-2 and MMP-9 by gelatin zymography and expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNAs were examined in 11 lung cancer cell lines which included six small-cell lung cancer (SCLC) cell lines. Localization of MMP-2, MMP-9, TIMP-1, and TIMP-2 was examined by immunohistochemistry in 43 resected NSCLC (22 adenocarcinomas, 17 squamous cell carcinomas, 4 large cell carcinomas) using specific anti-human monoclonal antibodies. Expression of MMP-2 mRNA was detected in 5 (100%), MMP-9 in 1 (20%), TIMP-1 in 4 (80%), and TIMP-2 in 5 (100%) of 5 NSCLC cell lines examined. MMP-2 gelatinolytic activity also was detected in all five NSCLC cell lines, whereas MMP-9 activity was detected in only one cell line. In 43 patients, MMP-2, MMP-9, TIMP-1, and TIMP-2 immunoreactivity was demonstrated in 19 (44%), 9 (21%), 15 (35%), and 29 (67%) excised tumors, respectively. All stromal fibroblasts in tumor samples stained positive for MMP-2. There was a correlation between TIMP-2 immunoreactivity and disease stage (42% stage I versus 88% stages II, III, and IV) (p = 0.0024). Both cancer cell lines and NSCLC tumor samples frequently expressed MMP-2, MMP-9, TIMP-1, and TIMP-2; MMP-2 in particular was highly expressed in malignant cells and surrounding fibroblasts. These findings suggest that MMP-2 plays a more important role in invasion of NSCLC than MMP-9 and that TIMP-2 may have clinical relevance in NSCLC.



Related Articles:

References

  1. Patterson PH: On the role of proteases, their inhibitors and the extracellullar matrix in promoting neurite outgrowth. J Physiol (Paris) 1985;80:207–211.
  2. Docherty AJP, O’Connell J, Crabbe T, Angal F, Murphy G: The matrix metalloproteinases and their natural inhibitors: Prospects for treating degenerative tissue diseases. Tibtech 1992;10:200–207.
  3. Woessner JF, Jr: Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 1991;5:2145–2154.
    External Resources
  4. Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S: Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 1980;284:67–68.
    External Resources
  5. Apdaca G, Rutka JT, Bouhana K, Berens ME, Giblin JR, Rosenblum ML, McKerrow JH, Banda MJ: Expression of metalloproteinases and metalloproteinase inhibitors by fetal astrocytes and glioma cells. Cancer Res 1990;50:2322–2329.
    External Resources
  6. Tryggvason K, Höyhtyä M, Pyke C: Type IV collagenases in invasive tumors. Breast Cancer Res Treat 1993;24:209–218.
    External Resources
  7. Gallegos NC, Smales C, Savage FJ, Hembry RM, Boulos PB: The distribution of matrix metalloproteinases and tissue inhibitor of metalloproteinases in colorectal cancer. Surg Oncol 1995;4:111–119.
    External Resources
  8. Iwata H, Kobayashi S, Iwase H, Masaoka A, Fujimoto N, Okada Y: Production of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human breast carcinomas. Jpn J Cancer Res 1996;87:602–611.
    External Resources
  9. Moll UM, Youngleib GL, Rosinski KB, Quigley JP: 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 1990;50:6162–6170.
    External Resources
  10. Liotta LA, Steeg PS, Stetler-Stevenson WG: Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell 1991;64:327–336.
    External Resources
  11. Klein-Szanto AJP, Iizasa T, Momiki S, Garcia-Palazzo I, Caamano J, Metcalf R, Welsh J, Harris CC: A tobacco-specific N-nitrosamine or cigarette smoke condensate causes neoplastic transformation of xenotransplanted human bronchial epithelial cells. Proc Natl Acad Sci USA 1992;89:6693–6697.
    External Resources
  12. Brown PD, Bloxidge RE, Stuart NSA, Gatter KC, Carmichael J: Association between expression of activated 72-kilodalton gelatinase and tumor spread in non-small-cell lung carcinoma. J Natl Cancer Inst 1993;85:574–578.
    External Resources
  13. Iizasa T, Momiki S, Bauer B, Caamano J, Metcalf R, Lechner J, Harris CC, Klein-Szanto AJP: Invasive tumors derived from xenotransplanted, immortalized human cells after in vivo exposure to chemical carcinogens. Carcinogenesis 1993;14:1789–1794.
    External Resources
  14. Kawahara E, Okada Y, Nakanishi I, Iwata K, Kojima S, Kumagai S, Yamamoto E: The expression of invasive behavior of differentiated squamous carcinoma cell line evaluated by an in vitro invasion model. Jpn J Cancer Res 1993;84:409–418.
    External Resources
  15. Brown PD, Bloxidge RE, Anderson E, Howell A: Expression of activated gelatinase in human invasive breast carcinoma. Clin Exp Metastasis 1993;11:183–189.
    External Resources
  16. Urbanski SJ, Edwards DR, Maitland A, Leco KJ, Watson A, Kossakowska AE: Expression of metalloproteinases and their inhibitors in primary pulmonary carcinomas. Br J Cancer 1992;66:1188–1194.
    External Resources
  17. Tolnay E, Wiethege T, Kuhnen C, Wulf M, Voss B, Muller KM: Expression of type IV collagenase correlates with the expression of vascular endothelial growth factor in primary non-small cell lung cancer. J Cancer Res Clin Oncol 1997;123:652–658.
    External Resources
  18. Clarke MR, Landreneau RJ, Finkelstein SD, We TT, Ohori P, Yousem SA: Extracellular matrix expression in metastasizing and nonmetastasizing adenocarcinomas of the lung. Hum Pathol 1997;28:54–59.
    External Resources
  19. American Joint Committee on Cancer: Manual for staging of cancer, ed 4. Philadelphia, Lippincott 1992, pp 115–122.
  20. The Japan Lung Cancer Society: The General Rules for Clinical and Pathological Record of Lung Cancer. Tokyo, Kanehara Press, 1995, pp 89–121.
  21. Heussen C, Dowdle EB: Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Anal Biochem 1980;102:196–202.
    External Resources
  22. Yamachika T, Nakanishi H, Inada K, Tsukamoto T, Kato T, Fukushima M, Inoue M, Tatematsu M: A new prognostic factor for colorectal carcinoma, thymidylate synthase, and its therapeutic significance. Cancer 1998;82:70–77.
    External Resources
  23. Kawano N, Osawa H, Ito T, Nagashima Y, Hirahara F, Inayama Y, Nakatani Y, Kimura S, Kitajima H, Koshikawa N, Miyazaki K, Kitamura H: Expression of gelatinase A, tissue inhibitor of metalloproteinases-2, matrilysin, and trypsin(ogen) in lung neoplasms: An immunohistochemical study. Hum Pathol 1997;28:613–622.
    External Resources
  24. Bissell DM, Friedman SL, Maher JJ, Roll FJ: Connective tissue biology and hepatic fibrosis: Report of a conference. Hepatology 1990;11:488–498.
    External Resources
  25. Nakajima M, Welch DR, Belloni PN, Nicolson GL: Degradation of basement membrane type IV collagen and lung subendothelial matrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res 1987;47:4869–4876.
    External Resources
  26. Yamagata S, Ito Y, Tanaka R, Tanaka R, Shimizu S: Gelatinases of metastatic cell lines of murine colonic carcinoma as detected by substrate-gel electrophoresis. Biochem Biophys Res Commun 1988;151:158–162.
    External Resources
  27. Sato H, Kida Y, Mai M, Endo Y, Sasaki T, Tanaka J, Seiki M: Expression of genes encoding type IV collagen-degrading metalloproteinases and tissue inhibitors of metalloproteinases in various human tumor cells. Oncogene 1992;7:77–83.
    External Resources
  28. Momiki S, Baba M, Caamano J, Iizasa T, Nakajima M, Yamaguchi Y, Klein-Szanto A: In vivo and in vitro invasiveness of human lung carcinoma cell lines. Invasion Metastasis 1991;11:66–75.
    External Resources
  29. Zucker S, Lysik RM, Malik M, Bauer BA, Caamano J, Klein-Szanto A: Secretion of gelatinases and tissue inhibitors of metalloproteinases by human lung cancer cell lines and revertant cell lines: not an invariant correlation with metastasis. Int J Cancer 1992;52:366–371.
    External Resources
  30. Gonzalez-Avila G, Iturria C, Vadillo F, Teran L, Selman M, Perez-Tamayo R: 72-kD (MMP-2) and 92-kD (MMP-9) type IV collagenase production and activity in different histologic types of lung cancer cells. Pathobiology 1998;66:5–16.
    External Resources
  31. Docherty AJP, Lyons A, Smith BJ, Wright EM, Stephens PE, Harris TJR: Sequence of human tissue inhibitor of metalloproteinases and its identity to erythroid-potentiating activity. Nature 1985;318:66–69.
    External Resources
  32. Stetler-Stevenson WG, Krutzsch HC, Liotta LA: Tissue inhibitor of metalloproteinase (TIMP-2). J Biol Chem 1989;264:17374–17378.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: August 25, 1999
Issue release date: August 1999

Number of Print Pages: 8
Number of Figures: 5
Number of Tables: 1

ISSN: 0251-1789 (Print)
eISSN: 1423-0119 (Online)

For additional information: https://www.karger.com/IAM

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Article Tools
Article Details

1998, Vol.18, No. 3

August 1999

Article

Recommend This
TOP