Journal Mobile Options
Table of Contents
Vol. 23, No. 3, 2002
Issue release date: May–June 2002 (September 2002)

Differential Expression and Activity Status of MMP-1, MMP-2 and MMP-9 in Tumor and Stromal Cells of Squamous Cell Carcinomas of the Lung

Schütz A. · Schneidenbach D. · Aust G. · Tannapfel A. · Steinert M. · Wittekind C.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Matrix metalloproteinases (MMPs) play a key role in cancer progression. Interstitial collagenase (MMP-1) and type IV collagenases (MMP-2, MMP-9) are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. Besides tumor cells, fibroblasts are especially involved in MMP production. The aim of this study was to quantify MMP-1, MMP-2 and MMP-9 within tumor cells and tumor-surrounding fibroblasts compared to normal lung epithelial cells to gain an insight into the function of these MMPs in squamous cell carcinomas of the lung. The expression and activity of MMP-1, MMP-2 and MMP-9 were analyzed in 30 squamous cell carcinomas and in normal lung tissue from the same patients by immunohistology and gelatin zymography. The majority of tumor cells were positive for MMP-1 (mean ± SD: 67.3 ± 26.7%) and MMP-9 (64.7 ± 22.8%), whereas a significantly lower percentage of normal bronchoepithelial cells (47.3 ± 25.4 and 40.3 ± 24.2%, respectively; p < 0.01) and fibroblasts located in the tumor-surrounding tissue (39.7 ± 14.3 and 38.1 ± 24.1%, respectively; p < 0.01) expressed these MMPs. Only a few tumor cells showed any immunoreactivity for MMP-2 (4.4 ± 6.7%), whereas a higher percentage of fibroblasts tested positive for this enzyme (8.6 ± 13.1%; p < 0.01). Using gelatin zymography, we could demonstrate that MMP-2 is activated in the tumor only, not in normal lung tissue. The coordinated expression of MMP-1, MMP-2 and MMP-9 in tumor cells and/or their induction in tumor-surrounding fibroblasts and further activation in the tumor tissue may be involved in the high invasive and metastatic potential of squamous cell carcinomas of the lung. Comparing the results from immunohistology and zymography can give indications for distribution and activity of proteinases, especially certain MMPs such as MMP-2.



Copyright / Drug Dosage

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.

References

  1. Stetler-Stevenson WG, Hewitt R, Corcoran M: Matrix metalloproteinases and tumor invasion: From correlation and causality to the clinic. Semin Cancer Biol 1996;7:147–154.

    External Resources

  2. McDonnell S, Fingleton B: Role of matrix metalloproteinases in invasion and metastasis: Biology, diagnosis and inhibitors. Cytotechnology 1993;12:367–384.

    External Resources

  3. Mari BP, Anderson IC, Mari SE, Ning Y, Lutz Y, Kobzik L, Shipp MA: Stromelysin-3 is induced in tumor/stroma cocultures and inactivated via a tumor-specific and basic fibroblast growth factor-dependent mechanism. J Biol Chem 1998;273:618–626.
  4. Goldberg GI, Wilhelm SM, Kronberger A, Bauer EA, Grant GA, Eisen AZ: Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein. J Biol Chem 1986;261:6600–6605.
  5. Nomura H, Fujimoto N, Seiki M, Mai M, Okada Y: Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas. Int J Cancer 1996;69:9–16.
  6. Murray GI, Duncan ME, O’Neil P, McKay JA, Melvin WT, Fothergill JE: Matrix metalloproteinase-1 is associated with poor prognosis in oesophageal cancer. J Pathol 1998;185:256–261.
  7. Onisto M, Garbisa S, Caenazzo C, Freda MP, Di Francesco C, Nitti D, Liotta LA, Stetler-Stevenson WG: Reverse transcription-polymerase chain reaction phenotyping of metalloproteinases and inhibitors involved in tumor matrix invasion. Diagn Mol Pathol 1993;2:74–80.
  8. Garzetti GG, Ciavattini A, Lucarini G, Goteri G, De Nictolis M, Romanini C, Biagini G: Recurrence patterns in locally advanced cervical carcinoma: Role of nodal status and 72-kDa metalloproteinase index. Gynecol Oncol 1996;61:83–89.
  9. Murray GI, Duncan ME, O’Neil P, Melvin WT, Fothergill JE: Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat Med 1996;2:461–462.
  10. Alessandro R, Minafra S, Pucci-Minafra I, Onisto M, Garbisa S, Melchiori A, Tetlow L, Woolley DE: Metalloproteinase and TIMP expression by the human breast carcinoma cell line 8701-BC. Int J Cancer 1993;55:250–255.
  11. Bramhall SR, Stamp GW, Dunn J, Lemoine NR, Neoptolemos JP: Expression of collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of the metalloproteinases (TIMP1) in pancreatic and ampullary disease. Br J Cancer 1996;73:972–978.
  12. Nakopoulou L, Giannopoulou I, Gakiopoulou H, Liapis H, Tzonou A, Davaris PS: Matrix metalloproteinase-1 and -3 in breast cancer: Correlation with progesterone receptors and other clinicopathologic features. Hum Pathol 1999;30:436–442.
  13. Tokuraku M, Sato H, Murakami S, Okada Y, Watanabe Y, Seiki M: Activation of the precursor of gelatinase A/72 kDa type IV collagenase/MMP-2 in lung carcinomas correlates with the expression of membrane-type matrix metalloproteinase (MT-MMP) and with lymph node metastasis. Int J Cancer 1995;64:355–359.
  14. Nawrocki B, Polette M, Marchand V, Monteau M, Gillery P, Tournier JM, Birembaut P: Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas: Quantificative and morphological analyses. Int J Cancer 1997;72:556–564.
  15. Nakagawa H, Yagihashi S: Expression of type IV collagen and its degrading enzymes in squamous cell carcinoma of lung. Jpn J Cancer Res 1994;85:934–938.
  16. Kodate M, Kasai T, Hashimoto H, Yasumoto K, Iwata Y, Manabe H: Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung. Pathol Int 1997;47:461–469.
  17. Thomas P, Khokha R, Shepherd FA, Feld R, Tsao MS: Differential expression of matrix metalloproteinases and their inhibitors in non-small cell lung cancer. J Pathol 2000;190:150–156.
  18. Collier IE, Wilhelm SM, Eisen AZ, Marmer BL, Grant GA, Seltzer JL, Kronberger A, He CS, Bauer EA, Goldberg GI: H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem 1988;263:6579–6587.
  19. Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant GA, Goldberg GI: 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 1989;264:17213–17221.
  20. Brown PD, Levy AT, Margulies IM, Liotta LA, Stetler-Stevenson WG: Independent expression and cellular processing of Mr 72,000 type IV collagenase and interstitial collagenase in human tumorigenic cell lines. Cancer Res 1990;50:6184–6191.
  21. Kleiner DE, Stetler-Stevenson WG: Quantitative zymography: Detection of picogram quantities of gelatinases. Anal Biochem 1994;218:325–329.
  22. Bodey B, Bodey BJ, Groger AM, Siegel SE, Kaiser HE: Invasion and metastasis: The expression and significance of matrix metalloproteinases in carcinomas of the lung. In Vivo 2000;15:175–180.
  23. Reichenberger F, Eickelberg O, Wyser C, Perruchoud AP, Roth M, Tamm M: Distinct endobronchial expression of matrix-metalloproteinases (MMP) and their endogenous inhibitors in lung cancer. Swiss Med Wkly 2001;131:273–279.

    External Resources

  24. Hofmann A, Laue S, Rost AK, Scherbaum WA, Aust G: mRNA levels of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, and MMP-9 and of their inhibitors TIMP-2 and TIMP-3 in normal thyrocytes and thyroid carcinoma cell lines. Thyroid 1998;8:203–214.

    External Resources

  25. Sato H, Seiki M: Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis. J Biochem 1996;119:209–215.
  26. Campo E, Merino MJ, Liotta L, Neumann R, Stetler-Stevenson W: Distribution of the 72-kd type IV collagenase in nonneoplastic and neoplastic thyroid tissue. Hum Pathol 1992;23:1395–1401.
  27. McDonnell S, Fingleton B: Role of matrix metalloproteinases in invasion and metastasis: Biology, diagnosis and inhibitors. Cytotechnology 1993;12:367–384.

    External Resources

  28. Kossakowska AE, Huchcroft SA, Urbanski SJ, Edwards DR: Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin’s lymphomas in humans. Br J Cancer 1996;73:1401–1408.
  29. Pritchard SC, Nicolson MC, Lloret C, McKay JA, Ross VG, Kerr KM, Murray GI, McLeod HL: Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: Implications for MMP inhibition therapy. Oncol Rep 2001;8:421–424.

    External Resources

  30. Aust G, Hofmann A, Laue S, Rost A, Kohler T, Scherbaum WA: Human thyroid carcinoma cell lines and normal thyrocytes: Expression and regulation of matrix metalloproteinase-1 and tissue matrix metalloproteinase inhibitor-1 messenger-RNA and protein. Thyroid 1997;7:713–724.

    External Resources



Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50