Journal Mobile Options
Table of Contents
Vol. 27, No. 3, 2006
Issue release date: May 2006

Matrix Metalloproteinases 21 and 26 Are Differentially Expressed in Esophageal Squamous Cell Cancer

Ahokas K. · Karjalainen-Lindsberg M.-L. · Sihvo E. · Isaka K. · Salo J. · Saarialho-Kere U.
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 metalloproteinase 21 (MMP-21) and MMP-26 (matrilysin-2) are the two newest members of the human MMP gene family that have both been suggested to play an important role in epithelial tumor progression and to be regulated via the Wnt signaling pathway. We studied their expression in 34 esophageal squamous cell carcinomas and non-neoplastic epithelium. MMP-21 protein was detected in cancer cells and inflammatory cells at the invasive front. Its expression was associated with invasion, inflammation, apoptotic and well-differentiated areas of the tumors, but not with cell proliferation. Unlike MMP-21, MMP-26 protein was already upregulated in incipient invasion and its expression associated with regions of low differentiation being more sporadic at the invasive front. MMP-21 was detected basally in KYSE-30 and OE21 esophageal squamous cell carcinoma cells, while MMP-26 was absent. None of the several cytokines and matrices tested were capable of consistently upregulating MMP-21 or MMP-26 mRNA expression in these two cell lines. Our results suggest that during esophageal tumorigenesis, MMP-21 and MMP-26 have different, unique expression patterns both being tightly regulated and induced in the vicinity of inflammation. MMP-21 may provide a marker for differentiating tumor areas. The putative role of MMP-26 as a marker of dysplasia and incipient invasion warrants further studies.



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. Launoy G, Milan CH, Faivre J, Pienkovski P, Milan CI, Gignoux M: Alcohol, tobacco and oesophageal cancer: effects of the duration of consumption, mean intake and current and former consumption. Br J Cancer 1997;75:1389–1396.
  2. Enzinger PC, Mayer RJ: Esophageal cancer. N Engl J Med 2003;349:2241–2252.
  3. Hamilton SR, Aaltonen LA (eds): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. Lyon, IARC Press, 2000.
  4. Hojilla CV, Mohammed FF, Khokha R: Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development. Br J Cancer 2003;89:1817–1821.
  5. Tanioka Y, Yoshida T, Yagawa T, Saiki Y, Takeo S, Harada T, Okazawa T, Yanai H, Okita K: Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer. Br J Cancer 2003;89:2116–2121.
  6. Etoh T, Inoue H, Yoshikawa Y, Barnard GF, Kitano S, Mori M: Increased expression of collagenase-3 (MMP-13) and MT1-MMP in oesophageal cancer is related to cancer aggressiveness. Gut 2000;47:50–56.
  7. Yamashita K, Tanaka Y, Mimori K, Inoue H, Mori M: Differential expression of MMP and uPA systems and prognostic relevance of their expression in esophageal squamous cell carcinoma. Int J Cancer 2004;110:201–207.
  8. Samantaray S, Sharma R, Chattopadhyaya TK, Datta Gupta S, Ralhan R: Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 2003;130:37–44.
  9. Ding Y, Shimada Y, Gorrin-Rivas MJ, Itami A, Li Z, Hong T, Maeda M, Komoto I, Kawabe A, Kaganoi J, Imamura M: Clinicopathological significance of human macrophage metalloelastase expression in esophageal squamous cell carcinoma. Oncology 2002;63:378–384.
  10. Ahokas K, Lohi J, Lohi H, Elomaa O, Karjalainen-Lindsberg ML, Kere J, Saarialho-Kere U: Matrix metalloproteinase-21, the human orthologue for XMMP, is expressed during fetal development and in cancer. Gene 2002;301:31–41.
  11. Overall C, Lopéz-Otín C: Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer 2002;2:657–672.
  12. Marchenko GN, Marchenko ND, Strongin AY: The human and mouse matrix metalloproteinase MMP-21: the structure and the regulation of the gene and the protein. Biochem J 2003;372:503–515.
  13. Ahokas K, Lohi J, Illman SA, Llano E, Impola U, Karjalainen-Lindsberg ML, Saarialho-Kere U: Matrix metalloproteinase-21 is expressed epithelially during development and in cancer and is upregulated by TGF-beta1 in keratinocytes. Lab Invest 2003;83:1887–1899.
  14. de Coignac AB, Elson G, Delneste Y, Magistrelli G, Jeannin P, Aubry JP, Berthier O, Schmitt D, Bonnefoy JY, Gauchat JF: Cloning of MMP-26. A novel matrilysin-like proteinase. Eur J Biochem 2000;267:3323–3329.
  15. Uría JA, López-Otín C: Matrilysin-2, a new matrix metalloproteinase expressed in human tumors and showing the minimal domain organization required for secretion, latency, and activity. Cancer Res 2000;60:4745–4751.
  16. Park HI, Ferry JN, Gerkema FE, Liu D, Belozerov VE, Sang QXA: Identification and characterization of human endometase (matrix metalloproteinase-26) from endometrial tumor. J Biol Chem 2000;275:20540–20544.
  17. Marchenko GN, Ratvnikov BI, Rozanov DV, Godzik A, Deryugina EI, Strongin AY: Characterization of matrix metalloproteinase-26, a novel metalloproteinase widely expressed in cancer cells of epithelial origin. Biochem J 2001;356:705–718.
  18. Park HI, Turk BE, Gerkema FE, Cantley LC, Sang QX: Peptide substrate specificities and protein cleavage sites of human endometase/matrilysin-2/matrix metalloproteinase-26. J Biol Chem 2002;277:35168–35175.
  19. Zhao YG, Xiao AZ, Newcomer RG, Park HI, Kang T, Chung LW, Swanson MG, Zhau HE, Kurhanewicz J, Sang QX: Activation of pro-gelatinase B by endometase/matrilysin-2 promotes invasion of human prostate cancer cells. J Biol Chem 2003;278:15056–15064.
  20. Zhao YG, Xiao AZ, Park HI, Newcomer RG, Yan M, Man YG, Heffelfinger SC, Sang QX: Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion. Cancer Res 2004;64:590–598.
  21. Tunuguntla R, Ripley D, Sang QXA, Chegini N: Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer. Gyn Oncol 2003;89:453–459.
  22. Isaka K, Nishi H, Nakai H, Nakada T, Li YF, Ebihara Y, Takayama M: Matrix metalloproteinase-26 is expressed in human endometrium but not in endometrial carcinoma. Cancer 2003;97:79–89.
  23. Pilka R, Whatling C, Domanski H, Hansson S, Eriksson P, Casslén B: Epithelial expression of matrix metalloproteinase-26 is elevated at mid-cycle in the human endometrium. Mol Hum Reprod 2003;9:271–277.
  24. Ahokas K, Skoog T, Suomela S, Jeskanen L, Impola U, Isaka K, Saarialho-Kere U: Matrilysin-2 (MMP-26) is upregulated in keratinocytes during wound repair and early skin carcinogenesis. J Invest Dermatol 2005;124:849–856.
  25. Sobin LH, Fleming ID: TNM classification of malignant tumors, fifth edition. Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer 1997;80:1803–1804.
  26. Shimada Y, Imamura M, Wagata T, Yamaguchi N, Tobe T: Characterization of 21 newly established esophageal cancer cell lines. Cancer 1992;69:277–284.
  27. Rockett JC, Larkin K, Darnton SJ, Morris AG, Matthews HR: Five newly established oesophageal carcinoma cell lines: phenotypic and immunological characterization. Br J Cancer 1997;75:258–263.
  28. Saarialho-Kere U, Kerkelä E, Jahkola T, Keski-Oja J, Lohi J: Epilysin (MMP-28) expression is associated with cell proliferation during epithelial repair. J Invest Dermatol 2002;119:14–21.
  29. Impola U, Uitto VJ, Hietanen J, Häkkinen L, Zhang L, Larjava H, Saarialho-Kere U: Differential expression of matrilysin-1 (MMP-7), 92 kDa gelatinase (MMP-9) and metalloelastase (MMP-12) in oral verrucous and squamous cell cancer. J Pathol2004;202:14–22.
  30. Pyke C, Salo S, Ralfkiaer E, Romer J, Dano K, Tryggvason K: Laminin-5 is a marker of invading cancer cells in some human carcinomas and is coexpressed with the receptor for urokinase plasminogen activator in budding cancer cells in colon adenocarcinomas. Cancer Res 1995;55:4132–4139.
  31. Airola K, Johansson N, Kariniemi AL, Kähäri VM, Saarialho-Kere UK: Human collagenase-3 is expressed in malignant squamous epithelium of the skin. J Invest Dermatol 1997;109:225–231.
  32. Yamamoto H, Vinitketkumnuen A, Adachi Y, Taniguchi H, Hirata T, Miyamoto N, Nosho K, Imsumran A, Fujita M, Hosokawa M, Hinoda Y, Imai K: Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma. Carcinogenesis 2004;25:2353–2360.
  33. Saeki H, Tanaka S, Sugimachi K, Kimura Y, Miyazaki M, Ohga T, Mugimachi K: Interrelation between expression of matrix metalloproteinase 7 and beta-catenin in esophageal cancer. Dig Dis Sci 2002;47:2738–2742.
  34. Balbin M, Fueyo A, Tester AM, Pendas AM, Pitiot AS, Astudillo A, Overall CM, Shapiro SD, Lopéz-Otín C: Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nat Genet 2003;35:252–257.
  35. Coussens LM, Tinkle CL, Hanahan D, Werb Z: MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 2000;103:481–490.
  36. Li W, Savinov AY, Rozanov DV, Golubkov VS, Hedayat H, Postnova TI, Golubkova NV, Linli Y, Krajewski S, Strongin AY: Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies and targets alpha1-antitrypsin serpin. Cancer Res 2004;64:8657–8665.


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