Skip to main content

Advertisement

SpringerLink
Log in

Knockdown of MMP-7 inhibits cell proliferation and enhances sensitivity to 5-fluorouracil and X-ray irradiation in colon cancer cells

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

The role of matrix metalloproteinase-7 (MMP-7) in the pathogenesis of colon cancer is not understood thoroughly. Previous studies from our group have shown that the expression levels of MMP-7 were highly elevated in colorectal cancer patient specimens and were correlated with Dukes Staging, histological differentiation grade and CEA level. The goal of this study was to investigate the cellular impact of MMP-7 in colon cancer. In this study, we used the SW480 colon cancer cell lines of MMP-7 knockdown by lentivirus-mediated RNA interference as a model system to investigate the impact of MMP-7 on cell proliferation and sensitivity to 5-Fluorouracil (5-FU) and X-ray irradiation (IR). Cell proliferation and sensitivity to 5-FU and IR were measured by MTT assay and colony formation assay. Cell cycle was evaluated by flow cytometry. We showed that the down regulation of MMP-7 inhibits colon cancer cell proliferation and sensitizes tumour cells to 5-FU and IR (P < 0.05). Decreased MMP-7 expression in SW480 cells by RNA interference triggered cell cycle arrest at G1 phase (P < 0.05). Down regulation of MMP-7 may inhibit the cell proliferation of colon cancer cells and increase tumour cells sensitivity to radiotherapy and chemotherapy. RNAi-mediated silencing of MMP-7 may represent a powerful therapeutic approach for controlling human colorectal cancer growth.

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

References

  1. Curran S, Murray GI (2000) Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer 36:1621–1630

    Article  CAS  PubMed  Google Scholar 

  2. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM (2000) Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 18:1135–1149

    CAS  PubMed  Google Scholar 

  3. Curran S, Murray GI (1999) Matrix metalloproteinases in tumour invasion and metastasis. J Pathol 189:300–308

    Article  CAS  PubMed  Google Scholar 

  4. Murray GI (2001) Matrix metalloproteinases: a multifunctional group of molecules. J Pathol 195:135–137

    Article  CAS  PubMed  Google Scholar 

  5. Jones LE, Humphreys MJ, Campbell F, Neoptolemos JP, Boyd MT (2004) Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: increased expression of matrix metalloproteinase-7 predicts poor survival. Clin Cancer Res 10:2832–2845

    Article  CAS  PubMed  Google Scholar 

  6. Saitoh Y, Yanai H, Higaki S, Nohara H, Yoshida T, Okita K (2004) Relationship between matrix metalloproteinase-7 and pit pattern in early stage colorectal cancer. Gastrointest Endosc 59:385–392

    Article  PubMed  Google Scholar 

  7. Luo H, Zhou Z, Yang L et al (2005) Clinicopathologic and prognostic significance of MMP-7 (Matrilysin) expression in human rectal cancer. Jpn J Clin Oncol 35(12):739–744

    Article  PubMed  Google Scholar 

  8. Coussens LM, Fingleton B, Matrisian LM (2002) Matrix metalloproteinases inhibitors and cancer: trials and tribulations. Science 295:2387–2391

    Article  CAS  PubMed  Google Scholar 

  9. Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161–174

    Article  CAS  PubMed  Google Scholar 

  10. Leeman MF, Curran S, Murray GI (2003) New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression. J Pathol 201:528–534

    Article  CAS  PubMed  Google Scholar 

  11. Rudolph-Owen LA, Chan R, Muller WJ, Matrisian LM (1998) The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis. Cancer Res 58:5500–5506

    CAS  PubMed  Google Scholar 

  12. Wilson CL, Heppner KJ, Labosky PA, Hogan BL, Matrisian LM (1997) Intestinal tumorigenesis is suppressed in mice lacking the metallo-proteinase matrilysin. Proc Natl Acad Sci USA 94:1402–1407

    Article  CAS  PubMed  Google Scholar 

  13. Almendro V, Ametller E, Garcı a-Recio S, Collazo O, Casas I et al (2009) The role of MMP7 and its cross-talk with the FAS/FASL system during the acquisition of chemoresistance to oxaliplatin. PLoS ONE 4(3):e4728

    Article  PubMed Central  PubMed  Google Scholar 

  14. Mitsiades N, Yu WH, Poulaki V, Tsokos M, Stamenkovic I (2001) Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity. Cancer Res 61:577–581

    CAS  PubMed  Google Scholar 

  15. Yamamoto H, Itoh F, Hinoda Y et al (1994) Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin. Biochem Biophys Res Commun 201:657–664

    Article  CAS  PubMed  Google Scholar 

  16. Fingleton BM, Heppner Goss KJ, Crawford HC, Matrisian LM (1999) Matrilysin in early stage intestinal tumorigenesis. APMIS 107:102–110

    Article  CAS  PubMed  Google Scholar 

  17. Heslin MJ, Yan J, Johnson MR, Weiss H, Diasio RB (2001) Role of matrix metalloproteinases in colorectal carcinogenesis. Ann Surg 233(6):786–792

    Article  CAS  PubMed  Google Scholar 

  18. Kitamura T, Biyajima K, Aoki M, Oshima M, Taketo MM (2009) Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas. Lab Invest 89:98–105

    Article  CAS  PubMed  Google Scholar 

  19. Brabletz T, Jung A, Dag S, Hlubek F, Kirchner T (1999) Beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol 155:1033–1038

    Article  CAS  PubMed  Google Scholar 

  20. Masaki T, Matsuoka H, Sugiyama M et al (2001) Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomas. Br J Cancer 84:1317–1321

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL, Gotlib J, Li K, Manz MG, Keating A, Sawyers CL, Weissman IL (2004) Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 351:657–667

    Article  CAS  PubMed  Google Scholar 

  22. Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM (2007) Wnt/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci USA 104:618–623

    Article  CAS  PubMed  Google Scholar 

  23. Klaus A, Birchmeier W (2008) Wnt signalling and its impact on development and cancer. Nat Rev Cancer 8:387–398

    Article  CAS  PubMed  Google Scholar 

  24. Chang HW, Roh JL, Jeong EJ, Lee SW, Kim SW, Choi SH, Park SK, Kim SY (2008) Wnt signaling controls radiosensitivity via cyclooxygenase-2-mediated Ku expression in head and neck cancer. Int J Cancer 122:100–107

    Article  CAS  PubMed  Google Scholar 

  25. Yang W, Yan HX, Chen L, Liu Q, He YQ, Yu LX, Zhang SH, Huang DD, Tang L, Kong XN, Chen C, Liu SQ, Wu MC, Wang HY (2008) Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Res 68:4287–4295

    Article  CAS  PubMed  Google Scholar 

  26. Ohigashi T, Mizuno R, Nakashima J, Marumo K, Murai M (2005) Inhibition of Wnt signaling downregulates Akt activity and induces chemosensitivity in PTEN-mutated prostate cancer cells. Prostate 62:61–68

    Article  CAS  PubMed  Google Scholar 

  27. Noda T, Nagano H, Takemasa I, Yoshioka S et al (2009) Activation of Wnt/b-catenin signaling pathway induces chemoresistance to interferon-a/5-fluorouracil combination therapy for hepatocellular carcinoma. Br J Cancer 100:1647–1658

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by National Science Foundation of China (No. 30830100) and PhD. Programs Foundation of Ministry of Education of China (No. 20080610058).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Institute of Digestive Surgery and Organ Microcirculation, West China Hospital, Sichuan University, No. 37 on Guo-Xue, Chengdu, 610041, Sichuan Provence, China

    Wei Zhang, Yuan Li, Lie Yang, Bin Zhou, Ke-Ling Chen, Wen-Jian Meng, Yong Liu, Jian-Kun Hu & Zong-Guang Zhou

  2. Department of Oncology, Linkoping University, Linköping, Sweden

    Xiao-Feng Sun

  3. National Key Labaratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

    Yuan Li, Bin Zhou, Ke-Ling Chen & Zong-Guang Zhou

Authors
  1. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lie Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ke-Ling Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wen-Jian Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jian-Kun Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiao-Feng Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zong-Guang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zong-Guang Zhou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, W., Li, Y., Yang, L. et al. Knockdown of MMP-7 inhibits cell proliferation and enhances sensitivity to 5-fluorouracil and X-ray irradiation in colon cancer cells. Clin Exp Med 14, 99–106 (2014). https://doi.org/10.1007/s10238-012-0212-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-012-0212-7

Keywords

Search

Navigation