Skip to main content

Advertisement

SpringerLink
Log in

Interaction of MT1-MMP and laminin-5γ2 chain correlates with metastasis and invasiveness in human esophageal squamous cell carcinoma

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

To gain insights into metastatic mechanisms in esophageal squamous cell carcinoma (ESCC), we established sublines (MLuB1 and MLuC1) with different capacity of spontaneous lung metastasis by subcutaneous injection of a human ESCC cell line (EC 9706) into nude mices. The incidence of the mice with lung metastasis produced by MLuC1 (87%) was significantly higher than that of MLuB1 (22%). The gene expression profiles of the two sublines were compared with cDNA arrays containing 5,000 known genes, and 47 genes were differentially expressed ≥2.0 fold. Laminin-5γ2 chain (Ln-5γ2) was one of the up-regulated genes in MLuC1 cells. Proteolytically processed forms of γ2 are known to promote migration of a multitude of epithelial cells in vitro. Western-blotting analysis revealed that degraded fragments of Ln-5γ2 and active form of membrane-type matrix metalloproteinase-1 (MT1-MMP) in MLuC1 was significantly higher than those in MLuB1. Expression of MT1-MMP was observed in 60 of 75 Ln-5γ2-positive carcinoma tissues (80%). Co-expression of the two proteins was significantly associated with depth of invasion (P = 0.012). Moreover, proteolytic fragments of Ln-5γ2 and active forms of MT1-MMP were frequently found in tumor tissues, whereas in the corresponding normal esophageal tissues there were only intact forms of γ2 and MT1-MMP. siRNA-mediated silencing of MT1-MMP significantly reduced production of γ2′ and γ2x in MLuC1 cells and inhibited cell migration. The results suggest that MT1-MMP is an enzyme responsible for Ln-5γ2 cleavage in ESCC, and interaction between them may play a critical role in promoting invasion and metastasis of human ESCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

Ln-5γ2:

Laminin-5γ2

MT1-MMP:

Membrane-type matrix metalloproteinase-1

ESCC:

Esophageal squamous cell carcinoma

GAPDH:

Glyceralde-3-phosphate dehydrogenase

CA12:

Carbonic anhydrase XII

HMGA2:

High mobility group AT-hook 2

CTSS:

Cathepsin S

COL4A6:

Collagen type IV alpha 6

COL7A1:

Collage type VII alpha 1

TSPAN-1:

Tetraspan 1

Reference

  1. Pisani P, Parkin DM, Bray F et al (1999) Estimates of the worldwide mortality from 25 cancers in. Int J Cancer 83:18–29

    Article  PubMed  CAS  Google Scholar 

  2. Pimkhaokham A, Shimada Y, Fukuda Y et al (2000) Nonrandom chromosomal imbalances in esophageal squamous cell carcinoma cell lines: possible involvement of the ATF3 and CENPF genes in the 1q32 amplicon. Jpn J Cancer Res 91:1126–1133

    PubMed  CAS  Google Scholar 

  3. Sugimachi K, Ohno S, Matsuda H et al (1988) Lugol-combined endoscopic detection of minute malignant lesions of the thoracic esophagus. Ann Surg 208:179–183

    Article  PubMed  CAS  Google Scholar 

  4. Ohashi K, Nemoto T, Nakamura K et al (2000) Increased expression of matrix metalloproteinase 7 and 9 and membrane type 1-matrix metalloproteinase in esophageal squamous cell carcinomas. Cancer 88:2201–2209

    Article  PubMed  CAS  Google Scholar 

  5. Peracchia A, Bonavina L, Ruol A et al (2000) Esophageal cancer: a European perspective. Recent Results Cancer Res 155:119–122

    PubMed  CAS  Google Scholar 

  6. Hirai T, Kuwahara M, Yoshida K et al (1998) Clinical results of transhiatal esophagectomy for carcinoma of the lower thoracic esophagus according to biological markers. Dis Esophagus 11:221–225

    PubMed  CAS  Google Scholar 

  7. Inada S, Koto T, Futami K et al (1999) Evaluation of malignancy and the prognosis of esophageal cancer based on an immunohistochemical study (p53, E-cadherin, epidermal growth factor receptor). Surg Today 29:493–503

    Article  PubMed  CAS  Google Scholar 

  8. Iihara K, Shiozaki H, Tahara H et al (1993) Prognostic significance of transforming growth factoralpha in human esophageal carcinoma. Implication for the autocrine proliferation. Cancer 71:2902–2909

    Article  PubMed  CAS  Google Scholar 

  9. Hollstein M, Sidransky D, Vogelstein B et al (1991) p53 mutations in human cancers. Science 253:49–53

    Article  PubMed  CAS  Google Scholar 

  10. Nakagawa H, Zukerberg L, Togawa K et al (1995) Human cyclin D1 oncogene and esophageal squamous cell carcinoma. Cancer 76:541–549

    Article  PubMed  CAS  Google Scholar 

  11. Natsugoe S, Xiangming C, Matsumoto M et al (2002) Smad4 and transforming growth factor?-1 expression in patients with squamous cell carcinoma of the esophagus. Clin Cancer Res 8:1838–1842

    PubMed  CAS  Google Scholar 

  12. Fukai Y, Fukuchi M, Masuda N et al (2003) Reduced expression of transforming growth factor-receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma. Int J Cancer 104:161–166

    Article  PubMed  CAS  Google Scholar 

  13. Yamamoto H, Itoh F, Iku S et al (2001) Expression of the gamma(2) chain of laminin-5 at the invasive front is associated with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Clin Cancer Res 7:896–900

    PubMed  CAS  Google Scholar 

  14. Koshikawa N, Giannelli G., Cirulli V et al (2000) Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5. J Cell Biol 148:615–624

    Article  PubMed  CAS  Google Scholar 

  15. Gilles C, Polette M, Coraux C et al (2001) Contribution of MT1-MMP and of human laminin-5 gamma2 chain degradation to mammary epithelial cell migration. J Cell Sci 114(Pt 16):2967–2976

    PubMed  CAS  Google Scholar 

  16. Koshikawa N, Schenk S, Moeckel G et al (2004) Proteolytic processing of laminin-5 by MT1-MMP in tissues and its effects on epithelial cell morphology. FASEB J 18:364–366

    PubMed  CAS  Google Scholar 

  17. Veitch DP, Nokelainen P, McGowan KA et al (2003) Mammalian tolloid metalloproteinase, and not matrix metalloprotease 2 or membrane type 1 metalloprotease, processes laminin-5 in keratinocytes and skin. J Biol Chem 278:15661–15668

    Article  PubMed  CAS  Google Scholar 

  18. Koshikawa N, Minegishi T, Sharabi A et al (2005) Membrane-type matrix metalloproteinase-1 (MT1-MMP) is a processing enzyme for human laminin gamma 2 chain. J Biol Chem 280:88–93

    PubMed  CAS  Google Scholar 

  19. Oku N, Sasabe E, Ueta E et al (2006) Tight junction protein claudin-1 enhances the invasive activity of oral squamous cell carcinoma cells by promoting cleavage of laminin-5 gamma2 chain via matrix metalloproteinase (MMP)-2 and membrane-type MMP-1. Cancer Res 66:5251–5257

    Article  PubMed  CAS  Google Scholar 

  20. Han Y, Wei F, Xu X et al (2002) Establishment and comparative genomic hybridization analysis of human esophageanl carcinomas cell line EC9706. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 19:455–457

    PubMed  CAS  Google Scholar 

  21. Mariadason JM, Corner GA, Augenlicht LH (2000) Genetic reprogramming in pathways of colonic cell maturation induced by short chain fatty acids: comparison with trichostatin A, sulindac, and curcumin and implications for chemoprevention of colon cancer. Cancer Res 60:4561–4572

    PubMed  CAS  Google Scholar 

  22. Mariadason JM, Arango D, Corner GA et al (2002) A gene expression profile that defines colon cell maturation in vitro. Cancer Res 62:4791–4804

    PubMed  CAS  Google Scholar 

  23. Katoh K, Nakanishi Y, Akimoto S et al (2002) Correlation between Laminin-5 γ2 Chain expression and epidermal growth factor receptor expression and its clinicopathological significance in squamous cell carcinoma of the tongue. Oncology 62:318–326

    Article  PubMed  CAS  Google Scholar 

  24. Moriya Y, Niki T, Yamada T et al (2001) Increased expression of laminin-5 and its prognostic significance in small-sized lung adenocarcinoma: an immunohistochemical analysis of 102 cases. Cancer 91:1129–1141

    Article  PubMed  CAS  Google Scholar 

  25. Elbashir SM, Harborth J, Weber K et al (2002) Analysis of gene function in somatic mammalian cells using small interfering RNAs. Method 26:199–213

    Article  CAS  Google Scholar 

  26. Hess KR, Zhang W, Baggerly KA et al (2001) Microarrays: handling the deluge of data and extracting reliable information. Trends Biotechnol 19:463–468

    Article  PubMed  CAS  Google Scholar 

  27. Butte A (2002) The use and analysis of microarray data. Nat Rev Drug Discov 1:951–960

    Article  PubMed  CAS  Google Scholar 

  28. Murray GI, Duncan ME, O’Neil P et al (1998) Matrix metalloproteinase-1 is associated with poor prognosis in oesophageal cancer. J Pathol 185:256–261

    Article  PubMed  CAS  Google Scholar 

  29. Simon-Assmann P, Kedinger M (1993) Heterotypic cellular cooperation in gut morphogenesis and differentiation. Semin Cell Biol 4:221–230

    Article  PubMed  CAS  Google Scholar 

  30. Mizushima H, Koshikawa N, Moriyama K (1998) Wide distribution of laminin-5 gamma 2 chain in basement membranes of various human tissues. Horm Res 50(Suppl 2):7–14

    Article  PubMed  CAS  Google Scholar 

  31. Katayama M, Sekiguchi K (2004) Laminin-5 in epithelial tumour invasion. J Mol Histol 35:277–286

    Article  PubMed  CAS  Google Scholar 

  32. Koshikawa N, Moriyama K, Takamura H et al (1999) Overexpression of laminin gamma2 chain monomer in invading gastric carcinoma cells. Cancer Res 59:5596–5601

    PubMed  CAS  Google Scholar 

  33. Lenander C, Habermann JK, Ost A et al (2001) Laminin-5 gamma 2 chain expression correlates with unfavorable prognosis in colon carcinomas. Anal Cell Pathol 22:201–209

    PubMed  CAS  Google Scholar 

  34. Aoki S, Nakanishi Y, Akimoto S (2002) Prognostic significance of laminin-5 gamma2 chain expression in colorectal carcinoma: immunohistochemical analysis of 103 cases. Dis Colon Rectum 45:1520–1527

    Article  PubMed  Google Scholar 

  35. Pyke C, Salo S, Ralfkaer E et al (1995) 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 55:4132–4139

    PubMed  CAS  Google Scholar 

  36. Soini Y, Maata M, Salo S et al (1996) Expression of laminin gamma 2 chain in pancreatic adenocarcinoma. J Pathol 180:290–294

    Article  PubMed  CAS  Google Scholar 

  37. Tani T, Karttunen T, Kiviluoto T (1996) Alpha 6 beta 4 integrin and newly deposited laminin-1 and laminin-5 from the adhesion mechanism of gastric carcinoma. Am J Pathol 149:781–793

    PubMed  CAS  Google Scholar 

  38. Etoh T, Inoue H, Yoshikawa Y et al (2000) Increased expression of collagenase-3 (MMP-13) and MT1-MMP in oesophageal cancer is related to cancer aggressiveness. Gut 47:50–56

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Supported by National Science Fund (30470969), State Key Basic Research Grant of China (2004CB518705, 2002CB513101), Specialized Research Fund for the Doctoral Program of Higher Education of China (20050023046) and Program for Changjiang Scholars and Innovative Research Team in University (IRT0416).

Author information

Authors and Affiliations

  1. State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China

    Xiao-Ming Shen, Yu-Peng Wu, Yan-Bin Feng, Man-Li Luo, Xiao-Li Du, Yu Zhang, Yan Cai, Xin Xu, Ya-Ling Han, Qi-Min Zhan & Ming-Rong Wang

  2. Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China

    Xun Zhang

Authors
  1. Xiao-Ming Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu-Peng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan-Bin Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Man-Li Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao-Li Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yan Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ya-Ling Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qi-Min Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ming-Rong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ming-Rong Wang.

Electronic supplementary material

Below is the link to the electronic supplementary material.

(DOC 50 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shen, XM., Wu, YP., Feng, YB. et al. Interaction of MT1-MMP and laminin-5γ2 chain correlates with metastasis and invasiveness in human esophageal squamous cell carcinoma. Clin Exp Metastasis 24, 541–550 (2007). https://doi.org/10.1007/s10585-007-9091-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-007-9091-9

Keywords

Search

Navigation