Skip to main content

Advertisement

SpringerLink
Log in

Expression of MMP-9 and WAVE3 in colorectal cancer and its relationship to clinicopathological features

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To investigate matrix metalloproteinase 9 (MMP-9) and WAVE3 expression in human colorectal cancer (CRC) and to evaluate their clinical significance.

Methods

We first performed real-time PCR to evaluate mRNA expression of MMP-9 and WAVE3 in 21 pairs of fresh CRC samples matched with adjacent normal mucosa. Then, MMP-9 and WAVE3 proteins were evaluated by immunohistochemistry on CRC tissue microarrays which included 216 CRC specimens and corresponding normal colorectal mucosa, and their correlation with clinicopathological factors and overall survival after surgery was evaluated.

Results

Both real-time PCR and immunohistochemistry evaluation have demonstrated that MMP-9 and WAVE3 were over-expressed in colorectal cancer tissues compared with normal mucosa (p < 0.001). MMP-9 expression was significantly higher in patients with low-grade differentiation and distant metastasis (p = 0.003 and p = 0.005, respectively), and patients with MMP-9-positive expression had a poorer prognosis (p = 0.008). However, patients with WAVE3-positive expression had a better prognosis (p = 0.039) and particularly favorable prognostic factors, including non-lymph node metastasis, non-distant metastasis, and early TNM stage (p = 0.029, 0.021, and 0.003, respectively). In addition, MMP-9-negative/WAVE3-positive patients had the best overall survival (p = 0.021). In multivariate survival analysis, MMP-9 expression and combined expression status of MMP-9/WAVE3 were identified as independent prognostic factors for CRC (p = 0.046 and p = 0.019, respectively).

Conclusions

Combined analysis of MMP-9 and WAVE3 has a significant value for assessing prognosis of CRC patients after surgery.

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

Similar content being viewed by others

References

  • Alkhateeb SS, Neill M, Bar-Moshe S, Rhijn BV, Kakiashvili DM, Fleshner N, Jewett M, Petein M, Schulman C, Hanna S, Bostrom PJ, Roumeguere T, Shariat SF, Rorive S, Zlotta AR (2011) Long-term prognostic value of the combination of EORTC risk group calculator and molecular markers in non-muscle-invasive bladder cancer patients treated with intravesical Bacille Calmette-Guerin. Urol Ann 3(3):119–126. doi:10.4103/0974-7796.84954

    Article  PubMed  CAS  Google Scholar 

  • Ambrosino C, Nebreda AR (2001) Cell cycle regulation by p38 MAP kinases. Biol Cell 93(1–2):47–51

    Article  PubMed  CAS  Google Scholar 

  • Bendardaf R, Buhmeida A, Hilska M, Laato M, Syrjanen S, Syrjanen K, Collan Y, Pyrhonen S (2010) MMP-9 (gelatinase B) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients. Cancer Invest 28(1):38–43. doi:10.3109/07357900802672761

    Article  PubMed  CAS  Google Scholar 

  • Bulavin DV, Fornace AJ Jr (2004) p38 MAP kinase’s emerging role as a tumor suppressor. Adv Cancer Res 92:95–118. doi:10.1016/s0065-230x(04)92005-2

    Article  PubMed  CAS  Google Scholar 

  • Chen F, Hanaoka N, Sato K, Fujinaga T, Sonobe M, Shoji T, Sakai H, Miyahara R, Bando T, Okubo K, Hirata T, Date H (2009) Prognostic factors of pulmonary metastasectomy for colorectal carcinomas. World J Surg 33(3):505–511. doi:10.1007/s00268-008-9875-3

    Article  PubMed  CAS  Google Scholar 

  • Coso OA, Chiariello M, Yu JC, Teramoto H, Crespo P, Xu N, Miki T, Gutkind JS (1995) The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 81(7):1137–1146

    Article  PubMed  CAS  Google Scholar 

  • Engel FB, Schebesta M, Duong MT, Lu G, Ren S, Madwed JB, Jiang H, Wang Y, Keating MT (2005) p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev 19(10):1175–1187. doi:10.1101/gad.1306705

    Article  PubMed  CAS  Google Scholar 

  • Fernando HS, Sanders AJ, Kynaston HG, Jiang WG (2008) WAVE1 is associated with invasiveness and growth of prostate cancer cells. J Urol 180(4):1515–1521. doi:10.1016/j.juro.2008.06.004

    Article  PubMed  CAS  Google Scholar 

  • Hui L, Bakiri L, Stepniak E, Wagner EF (2007) p38alpha: a suppressor of cell proliferation and tumorigenesis. Cell Cycle 6(20):2429–2433

    Article  PubMed  CAS  Google Scholar 

  • International Agency for Research on Cancer (IARC) (2010). Available from: http://www-depiarcfr/

  • Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141(1):52–67. doi:10.1016/j.cell.2010.03.015

    Article  PubMed  CAS  Google Scholar 

  • Kim JH, Pyun JA, Lee KJ, Cho SW, Kwack KB (2011) Study on association between single nucleotide polymorphisms of MMP7, MMP8, MMP9 genes and development of gastric cancer and lymph node metastasis. Korean J Gastroenterol 58(5):245–251. doi:10.4166/kjg.2011.58.5.245

    Article  PubMed  CAS  Google Scholar 

  • Kupferman ME, Fini ME, Muller WJ, Weber R, Cheng Y, Muschel RJ (2000) Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression. Am J Pathol 157(6):1777–1783. doi:10.1016/s0002-9440(10)64815-8

    Article  PubMed  CAS  Google Scholar 

  • Kurisu S, Suetsugu S, Yamazaki D, Yamaguchi H, Takenawa T (2005) Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells. Oncogene 24(8):1309–1319. doi:10.1038/sj.onc.1208177

    Article  PubMed  CAS  Google Scholar 

  • Lee RJ, Albanese C, Stenger RJ, Watanabe G, Inghirami G, Haines GK, 3rd, Webster M, Muller WJ, Brugge JS, Davis RJ, Pestell RG (1999) pp60 (v-src) induction of cyclin D1 requires collaborative interactions between the extracellular signal-regulated kinase, p38, and Jun kinase pathways. A role for cAMP response element-binding protein and activating transcription factor-2 in pp60 (v-src) signaling in breast cancer cells. J Biol Chem 274(11):7341–7350

    Google Scholar 

  • Li J, Lau GK, Chen L, Dong SS, Lan HY, Huang XR, Li Y, Luk JM, Yuan YF, Guan XY (2011) Interleukin 17A promotes hepatocellular carcinoma metastasis via NF-kB induced matrix metalloproteinases 2 and 9 expression. PLoS One 6(7):e21816. doi:10.1371/journal.pone.0021816

    Article  PubMed  CAS  Google Scholar 

  • Mahmoud N, Bullard Dunn K (2010) Metastasectomy for stage IV colorectal cancer. Dis Colon Rectum 53(7):1080–1092. doi:10.1007/DCR.0b013e3181dcadbc

    Article  PubMed  Google Scholar 

  • Malliri A, van Es S, Huveneers S, Collard JG (2004) The Rac exchange factor Tiam1 is required for the establishment and maintenance of cadherin-based adhesions. J Biol Chem 279(29):30092–30098. doi:10.1074/jbc.M401192200

    Article  PubMed  CAS  Google Scholar 

  • Martin TA, Pereira G, Watkins G, Mansel RE, Jiang WG (2008) N-WASP is a putative tumour suppressor in breast cancer cells, in vitro and in vivo, and is associated with clinical outcome in patients with breast cancer. Clin Exp Metastasis 25(2):97–108. doi:10.1007/s10585-007-9120-8

    Article  PubMed  CAS  Google Scholar 

  • Mikami S, Katsube K, Oya M, Ishida M, Kosaka T, Mizuno R, Mukai M, Okada Y (2011) Expression of Snail and Slug in renal cell carcinoma: E-cadherin repressor Snail is associated with cancer invasion and prognosis. Lab Invest 91(10):1443–1458. doi:10.1038/labinvest.2011.111

    Article  PubMed  CAS  Google Scholar 

  • Miki H, Fukuda M, Nishida E, Takenawa T (1999) Phosphorylation of WAVE downstream of mitogen-activated protein kinase signaling. J Biol Chem 274(39):27605–27609

    Article  PubMed  CAS  Google Scholar 

  • Millard TH, Sharp SJ, Machesky LM (2004) Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex. Biochem J 380(Pt 1):1–17. doi:10.1042/bj20040176

    Article  PubMed  CAS  Google Scholar 

  • Minden A, Karin M (1997) Regulation and function of the JNK subgroup of MAP kinases. Biochim Biophys Acta 1333(2):F85–104

    PubMed  CAS  Google Scholar 

  • O’Connell JB, Maggard MA, Ko CY (2004) Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst 96(19):1420–1425. doi:10.1093/jnci/djh275

    Article  PubMed  Google Scholar 

  • Park KS, Kim SJ, Kim KH, Kim JC (2011) Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer. J Gastroenterol Hepatol 26(2):391–397. doi:10.1111/j.1440-1746.2010.06504.x

    Article  PubMed  CAS  Google Scholar 

  • Recio JA, Merlino G (2002) Hepatocyte growth factor/scatter factor activates proliferation in melanoma cells through p38 MAPK, ATF-2 and cyclin D1. Oncogene 21(7):1000–1008. doi:10.1038/sj.onc.1205150

    Article  PubMed  CAS  Google Scholar 

  • Ricote M, Garcia-Tunon I, Bethencourt F, Fraile B, Onsurbe P, Paniagua R, Royuela M (2006) The p38 transduction pathway in prostatic neoplasia. J Pathol 208(3):401–407. doi:10.1002/path.1910

    Article  PubMed  CAS  Google Scholar 

  • Roy R, Yang J, Moses MA (2009) Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 27(31):5287–5297. doi:10.1200/jco.2009.23.5556

    Article  PubMed  CAS  Google Scholar 

  • Sossey-Alaoui K, Su G, Malaj E, Roe B, Cowell JK (2002) WAVE3, an actin-polymerization gene, is truncated and inactivated as a result of a constitutional t (1:13) (q21:q12) chromosome translocation in a patient with ganglioneuroblastoma. Oncogene 21(38):5967–5974. doi:10.1038/sj.onc.1205734

    Article  PubMed  CAS  Google Scholar 

  • Sossey-Alaoui K, Ranalli TA, Li X, Bakin AV, Cowell JK (2005) WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression. Exp Cell Res 308(1):135–145. doi:10.1016/j.yexcr.2005.04.011

    Article  PubMed  CAS  Google Scholar 

  • Sossey-Alaoui K, Safina A, Li X, Vaughan MM, Hicks DG, Bakin AV, Cowell JK (2007) Down-regulation of WAVE3, a metastasis promoter gene, inhibits invasion and metastasis of breast cancer cells. Am J Pathol 170(6):2112–2121. doi:10.2353/ajpath.2007.060975

    Article  PubMed  CAS  Google Scholar 

  • Sossey-Alaoui K, Bialkowska K, Plow EF (2009) The miR200 family of microRNAs regulates WAVE3-dependent cancer cell invasion. J Biol Chem 284(48):33019–33029. doi:10.1074/jbc.M109.034553

    Article  PubMed  CAS  Google Scholar 

  • Sternlicht MD, Werb Z (1999) Guidebook to the extracellular matrix, anchor, and adhesion proteins. Sambrook. Oxford University Press, London, pp 519–538

    Google Scholar 

  • Suetsugu S, Takenawa T (2003) Regulation of cortical actin networks in cell migration. Int Rev Cytol 229:245–286

    Article  PubMed  CAS  Google Scholar 

  • Suetsugu S, Yamazaki D, Kurisu S, Takenawa T (2003) Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration. Dev Cell 5(4):595–609. doi:10.1016/S1534-5807(03)00297-1

    Article  PubMed  CAS  Google Scholar 

  • Teng Y, Ren MQ, Cheney R, Sharma S, Cowell JK (2010) Inactivation of the WASF3 gene in prostate cancer cells leads to suppression of tumorigenicity and metastases. Br J Cancer 103(7):1066–1075. doi:10.1038/sj.bjc.6605850

    Article  PubMed  CAS  Google Scholar 

  • Teng Y, Liu M, Cowell JK (2011) Functional interrelationship between the WASF3 and KISS1 metastasis-associated genes in breast cancer cells. Int J Cancer 129(12):2825–2835. doi:10.1002/ijc.25964

    Article  PubMed  CAS  Google Scholar 

  • Thornton TM, Rincon M (2009) Non-classical p38 map kinase functions: cell cycle checkpoints and survival. Int J Biol Sci 5(1):44–51

    Article  PubMed  CAS  Google Scholar 

  • Wagner EF, Nebreda AR (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9(8):537–549. doi:10.1038/nrc2694

    Article  PubMed  CAS  Google Scholar 

  • Wang W, Goswami S, Lapidus K, Wells AL, Wyckoff JB, Sahai E, Singer RH, Segall JE, Condeelis JS (2004) Identification and testing of a gene expression signature of invasive carcinoma cells within primary mammary tumors. Cancer Res 64(23):8585–8594. doi:10.1158/0008-5472.can-04-1136

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by National Basic Research Program of China (973 Program, No 2010CB529403), Key Project of Capital Medical Development Fund (2009–2095), Beijing Academic Leaders Program (2009-2-18), Beijing Municipal Natural Science Foundation (7122030), Capital characteristic clinical application study special project (Z121107001012083), and Grant of Beijing Cancer Hospital (10-04).

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Hepato-Pancreato-Biliary Surgery, Peking University School of Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing, 100142, China

    Yi Zhang, Xiao-Ya Guan, Jian-Hui Wu, Xiu-Yun Tian & Chun-Yi Hao

  2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Center Laboratory, Peking University School of Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing, 100142, China

    Bin Dong & Min Zhao

Authors
  1. Yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Ya Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Min Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Hui Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiu-Yun Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chun-Yi Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiu-Yun Tian or Chun-Yi Hao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, Y., Guan, XY., Dong, B. et al. Expression of MMP-9 and WAVE3 in colorectal cancer and its relationship to clinicopathological features. J Cancer Res Clin Oncol 138, 2035–2044 (2012). https://doi.org/10.1007/s00432-012-1274-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-012-1274-3

Keywords

Search

Navigation