Skip to main content
Log in

Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancer

  • Original Contributions
  • Published:
Diseases of the Colon & Rectum

Abstract

PURPOSE: Membrane-type matrix metalloproteinases are recently described proteolytic enzymes belonging to the matrix metalloproteinase family. Initial studies have indicated that membrane-type matrix metalloproteinases are involved in tumor invasion and metastasis. Membrane-type 1 matrix metalloproteinase is the first membrane-type matrix metalloproteinase to be described. The aim of this study was to investigate the expression of membrane-type 1 matrix metalloproteinase mRNA in colorectal cancer. METHODS: Samples were collected from surgical specimens of patients with colorectal adenocarcinoma and were immediately frozen in liquid nitrogen and stored at −80°C until processed. Both normal and cancer tissue was taken from each patient. TNM stage, tumor differentiation, mucin production, and vascular invasion were assessed. Northern blotting was used to quantify membrane-type 1 matrix metalloproteinase mRNA levels in the samples using a membrane-type 1 matrix metalloproteinase cDNA clone. X-ray film images were digitized and densitometry was used to quantify bands. All samples were normalized against 18S rRNA levels. Results are expressed as the ratio of cancer to normal tissue levels. Statistical analysis was performed using analysis of variance, withP<0.05 accepted as the level of significance. RESULTS: A total of 32 samples were prospectively analyzed. The correlation between TNM stage and increased expression of membrane-type 1 matrix metalloproteinase mRNA in cancer tissue over normal tissue is expressed in the mean ratio of cancer to normal tissue expression for Stages I through IV, respectively: 1.4 ± 0.2 (12 patients); 4.1 ± 2.6 (8 patients); 3.4 ± 3 (7 patients); and 4.5 ± 5 (5 patients). Stage I is significantly different from Stages II and IV (P<0.05). These preliminary results show an overall increasing trend in membrane-type 1 matrix metalloproteinase expression with increasing tumor stage. However, there was no correlation between membrane-type 1 matrix metalloproteinase expression and mucin production, degree of tumor differentiation, or vascular invasion. CONCLUSION: Preliminary results indicate that membrane-type 1 matrix metalloproteinase levels correlate with increasing tumor stage.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sato H, Takino T, Okada Y,et al. A matrix metalloproteinase expressed on the cell surface of invasive tumor cells. Nature 1994;370:61–5.

    Article  PubMed  Google Scholar 

  2. Atkinson SJ, Crabbe T, Cowell S,et al. Intermolecular autolytic cleavage can contribute to the activation of progelatinase A by cell membranes. J Biol Chem 1995;270:30479–85.

    Article  PubMed  Google Scholar 

  3. Baramova EN, Munaut C, Remacle A, Pichot B, Foidart JM. Correlation of tumor cells membrane activation of gelatinase A with the expression of MT-MMP m RNA. Cell Biol Int 1995;19:248.

    Google Scholar 

  4. Cao J, Sato H, Takino T, Seiki M. The C-terminal region of membrane type matrix metalloproteinase is a functional transmembrane domain required for progelatinase A activation. J Biol Chem 1995;270:801–5.

    Article  PubMed  Google Scholar 

  5. MacDougall JR, Matrisian LM. Contributions of tumor and stromal matrix metalloproteinases to tumor progression, invasion and metastasis. Cancer Metastasis Rev 1995;4:531–2.

    Google Scholar 

  6. Nomura H, Sato H, Seiki M, Mai M, Okada Y. Expression of membrane-type matrix metalloproteinase in human gastric carcinomas. Cancer Res 1995;55:3263–6.

    PubMed  Google Scholar 

  7. Tokuraku M, Sato H, Murakami S, Okada Y, Watanabe Y, Seiki M. Activation of the precursor of gelatinase A/72kDa type IV collagenase/MMP-2 in lung carcinomas correlates with the expression of membrane-type matrix metalloproteinase (MT-MMP) and lymph node metastasis. Int J Cancer 1995;64:355–9.

    PubMed  Google Scholar 

  8. Fishman DA, Bafetti LM, Stack MS. Membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2 activation in primary human ovarian epithelial carcinoma cells. Invasion Metastasis 1996;16:150–9.

    PubMed  Google Scholar 

  9. Knauper V, Will H, Lopez-Otin C,et al. Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase A (MMP-2) are able to generate active enzyme. J Biol Chem 1996;271:17124–31.

    Article  PubMed  Google Scholar 

  10. d'Ortho MP, Will H, Atkinson S,et al. Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases. Eur J Biochem 1997;250:751–7.

    Article  PubMed  Google Scholar 

  11. Ohuchi E, Imai K, Fujii Y, Sato H, Seiki M, Okada Y. Membrane-type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem 1997;272:2446–51.

    PubMed  Google Scholar 

  12. Nakahara H, Howard L, Thompson EW,et al. Transmembrane cytoplasmic domain-mediated membrane-type 1 matrix metalloproteinase docking to invadopodia is required for cell invasion. Proc Natl Acad Sci U S A 1997;94:7959–64.

    Article  PubMed  Google Scholar 

  13. Nawrocki B, Polette M, Marchand V,et al. Membrane-type matrix metalloproteinase-1 expression at the site of human placentation. Placenta 1996;17:565–72.

    Article  PubMed  Google Scholar 

  14. Hurskainen T, Seiki M, Apte SS,et al. Production of membrane-type matrix metalloproteinase-1 (MT1-MMP) in early human placenta—a possible role in placental implantation. J Histochem Cytochem 1998;46:221–9.

    PubMed  Google Scholar 

  15. Tanaka SS, Mariko Y, Mori H,et al. Cell-cell contact down regulates expression of membrane-type matrix metalloproteinase-1 (MT1-MMP) in a mouse mammary gland epithelial cell line. Zool Sci 1997;14:95–9.

    PubMed  Google Scholar 

  16. Okada A, Bellocq JP, Rouyer N,et al. Membrane-type matrix metalloproteinase (M-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci U S A 1995;92:2730–4.

    PubMed  Google Scholar 

  17. Gilles C, Polette M, Piette J,et al. High level of MT-MMP expression is associated with invasiveness of cervical cancer cells. Int J Cancer 1996;65:209–13.

    Article  PubMed  Google Scholar 

  18. Ohtani H, Motohashi H, Sato H, Seiki M, Nagura H. Dual over-expression pattern of membrane-type matrix metalloprteinase-1 in cancer and stromal cells in human gastrointestinal carcinoma revealed by in situ hybridization and immunoelectron microscopy. Int J Cancer 1996;68:564–70.

    Article  Google Scholar 

  19. Mori M, Mimori K, Shiraishi T,et al. Analysis of MT1-MMP and MT2-MMP expression in human gastric cancers. Int J Cancer 1997;74:316–21.

    Article  PubMed  Google Scholar 

  20. Yammamoto H, Itoh F, Adachi Y,et al. Relation of enhanced secretion of active matrix metalloproteinases with tumor spread hepatocellular carcinoma. Gastroenterology 1997;112:1290–6.

    Article  PubMed  Google Scholar 

  21. Nawrocki B, Polette M, Marchand V,et al. Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas—quantitative and morphological analyses. Int J Cancer 1997;72:556–64.

    Article  PubMed  Google Scholar 

  22. Ueno H, Nakamura H, Inoue M,et al. Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas. Cancer Res 1997;57:2055–60.

    PubMed  Google Scholar 

  23. Harada T, Arii S, Mise M,et al. Membrane-type matrix metalloproteinase-1 (MT1-MMP) gene is overexpressed in highly invasive hepatocellular carcinomas. J Hepatol 1998;28:231–9.

    Article  PubMed  Google Scholar 

  24. Polette M, Nawrocki B, Gilles C,et al. MT-MMP expression and localization in human lung and breast cancers. Virchows Arch 1996;428:29–35.

    Article  PubMed  Google Scholar 

  25. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–9.

    Article  PubMed  Google Scholar 

  26. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual. 2nd ed. Cold Springs Harbor: Cold Springs Harbor Laboratory Press, 1989.

    Google Scholar 

  27. Tsujii M, Kawano S, DuBois RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A 1997;94:3336–40.

    Article  PubMed  Google Scholar 

  28. Williams CS, Smalley W, DuBois, RN. Aspirin use and potential mechanisms for colorectal cancer prevention. J Clin Invest 1997;100:1325–9.

    PubMed  Google Scholar 

  29. Giardiello FM, Offerhaus GJ, DuBois RN. The role of nonsteroidal anti-inflammatory drugs in colorectal cancer prevention. Eur J Cancer 1995;31A:1071–6.

    Article  PubMed  Google Scholar 

  30. Gann PH, Manson JE, Glynn RJ, Buring JE, Hennekens CH. Low-dose aspirin and incidence of colorectal tumors in a randomized trial. J Natl Cancer Inst 1993;85:1220–4.

    PubMed  Google Scholar 

  31. Nugent KP, Farmer KC, Spigelman AD, Williams CB, Phillips RK. Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis. Br J Surg 1993;80:1618–9.

    PubMed  Google Scholar 

  32. Sato H, Seiki M. Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis. J Biochem 1996;119:209–15.

    PubMed  Google Scholar 

  33. Stetler-Stevenson WG, Hewitt R, Corcoran M. Matrix metalloproteinases and tumor invasion: from correlation causality to the clinic. Semin Cancer Biol 1996;7:147–54.

    Article  PubMed  Google Scholar 

  34. Tsunezuka Y, Kinoh H, Takino T,et al. Expression of membrane-type matrix metalloproteinase-1 (MT-1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay. Cancer Res 1996;56:5678–83.

    PubMed  Google Scholar 

  35. Jones JL, Walker RA. Control of matrix metalloproteinase activity in cancer. J Pathol 1997;183:377–9.

    Article  PubMed  Google Scholar 

  36. Chapius PH, Dent OF, Fisher R,et al. A multivariate analysis of clinical and pathological variables in prognosis after resection of large bowel cancer. Br J Surg 1985;72:698–702.

    PubMed  Google Scholar 

  37. Minsky BD, Mies C, Rich TA, Recht A, Chaffey JT. Potential curative surgery of colon cancer: patterns of failure and survival. J Clin Oncol 1988;6:106–18.

    PubMed  Google Scholar 

  38. Griffin MR, Bergstralh EJ, Coffey RJ, Beart RW Jr, Melton LJ III. Predictors of survival after curative resection of carcinoma of the colon and rectum. Cancer 1987;60:2318–24.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported in part by a research grant from the David G. Jagelman memorial research fund.

Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.

About this article

Cite this article

Sardinha, T.C., Nogueras, J.J., Xiong, H. et al. Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancer. Dis Colon Rectum 43, 389–395 (2000). https://doi.org/10.1007/BF02258307

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02258307

Key words

Navigation