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.

  • Letter to the Editor
  • Published:

Matriptase is highly upregulated in chronic lymphocytic leukemia and promotes cancer cell invasion

Leukemia volume 27, pages 1191–1194 (2013)Cite this article

Subjects

Matriptase, also called MT-SP1 or epithin, is a type-II transmembrane serine protease expressed on the surface of the normal epithelium.1, 2 The enzyme is required for epidermal differentiation and barrier function in the skin. Low levels of matriptase mRNA also were detected in human blood cells including monocytes and B lymphocytes,3 but the biological significance of such expression is unclear. In monocytes, matriptase may be involved in initiating plasminogen activation.3

Studies indicate that matriptase may have an important role in cancer. Matriptase overexpression has been reported in many human solid tumors, including prostate, breast, ovarian, kidney and lung cancers.4, 5 In mice, transgenic matriptase expression in keratinocytes causes skin carcinoma.6 The molecular mechanism under which matriptase may participate in cancer is not fully understood. Matriptase has been shown to activate pro-urokinase, prostasin, protease-activated receptor-2, pro-hepatocyte growth factor, pro-macrophage stimulating protein-1, platelet-derived growth factor, vascular endothelial growth factor receptor 2 and Tie2 receptor.2, 4, 7, 8, 9 It is possible that these matriptase activities may promote cancer growth and invasion.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Lin CY, Tseng IC, Chou FP, Su SF, Chen YW, Johnson MD et al. Zymogen activation, inhibition, and ectodomain shedding of matriptase. Front Biosci 2008; 13: 621–635.

    Article  CAS  Google Scholar 

  2. Szabo R, Bugge TH . Membrane-anchored serine proteases in vertebrate cell and developmental biology. Annu Rev Cell Dev Biol 2011; 27: 213–235.

    Article  CAS  Google Scholar 

  3. Kilpatrick LM, Harris RL, Owen KA, Bass R, Ghorayeb C, Bar-Or A et al. Initiation of plasminogen activation on the surface of monocytes expressing the type II transmembrane serine protease matriptase. Blood 2006; 108: 2616–2623.

    Article  CAS  Google Scholar 

  4. Darragh MR, Bhatt AS, Craik CS . MT-SP1 proteolysis and regulation of cell-microenvironment interactions. Front Biosci 2008; 13: 528–539.

    Article  CAS  Google Scholar 

  5. List K . Matriptase: a culprit in cancer? Future Oncol 2009; 5: 97–104.

    Article  CAS  Google Scholar 

  6. List K, Szabo R, Molinolo A, Sriuranpong V, Redeye V, Murdock T et al. Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation. Genes Dev 2005; 19: 1934–1950.

    Article  CAS  Google Scholar 

  7. Kim C, Lee HS, Lee D, Lee SD, Cho EG, Yang SJ et al. Epithin/PRSS14 proteolytically regulates angiopoietin receptor Tie2 during transendothelial migration. Blood 2011; 117: 1415–1424.

    Article  CAS  Google Scholar 

  8. Lee SL, Dickson RB, Lin CY . Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. J Biol Chem 2000; 275: 36720–36725.

    Article  CAS  Google Scholar 

  9. Ustach CV, Huang W, Conley-LaComb MK, Lin CY, Che M, Abrams J et al. A novel signaling axis of matriptase/PDGF-D/ss-PDGFR in human prostate cancer. Cancer Res 2010; 70: 9631–9640.

    Article  CAS  Google Scholar 

  10. Bugge TH, Antalis TM, Wu Q . Type II transmembrane serine proteases. J Biol Chem 2009; 284: 23177–23181.

    Article  CAS  Google Scholar 

  11. Baba T, Kawaguchi M, Fukushima T, Sato Y, Orikawa H, Yorita K et al. Loss of membrane-bound serine protease inhibitor HAI-1 induces oral squamous cell carcinoma cells invasiveness. J Pathol 2012; 228: 181–192.

    Article  CAS  Google Scholar 

  12. Xu H, Xu Z, Tseng IC, Chou FP, Chen YW, Wang JK et al. Mechanisms for the control of matriptase activity in the absence of sufficient HAI-1. Am J Physiol Cell Physiol 2012; 302: C453–C462.

    Article  CAS  Google Scholar 

  13. Kirchhofer D, Peek M, Li W, Stamos J, Eigenbrot C, Kadkhodayan S et al. Tissue expression, protease specificity, and Kunitz domain functions of hepatocyte growth factor activator inhibitor-1B (HAI-1B), a new splice variant of HAI-1. J Biol Chem 2003; 278: 36341–36349.

    Article  CAS  Google Scholar 

  14. Egeblad M, Werb Z . New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002; 2: 161–174.

    Article  CAS  Google Scholar 

  15. Lopez-Otin C, Matrisian LM . Emerging roles of proteases in tumour suppression. Nat Rev Cancer 2007; 7: 800–808.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported in part by grants from the National Natural Science Foundation of China (31070716, 81170247 and 31161130356) and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Author Contributions

LG, ML and ND designed and performed experiments and wrote the paper. YJ performed experiments. C-YL and MH provided key reagents. DW provided clinical samples. QW designed experiments and wrote the paper; all authors participated in discussions and critically read the manuscript.

Author information

Author notes

  1. L Gao and M Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. The Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, China

    L Gao, M Liu, N Dong, Y Jiang & Q Wu

  2. Thrombosis and Hemostasis Key Laboratory of the Ministry of Health, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China

    N Dong & D Wu

  3. Lombardi Comprehensive Cancer Center, Georgetown University, School of Medicine, Washington, DC, USA

    C-Y Lin

  4. State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, China

    M Huang

  5. Danish-Chinese Center of Proteases and Cancer, Cleveland, OH, USA

    M Huang & Q Wu

  6. Molecular Cardiology, Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH, USA

    Q Wu

Authors
  1. L Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C-Y Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Q Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to D Wu or Q Wu.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gao, L., Liu, M., Dong, N. et al. Matriptase is highly upregulated in chronic lymphocytic leukemia and promotes cancer cell invasion. Leukemia 27, 1191–1194 (2013). https://doi.org/10.1038/leu.2012.289

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2012.289

This article is cited by

Search

Advanced search

Quick links