Article Data

  • Views 445
  • Dowloads 134

Original Research

Open Access

Stromal cells play a role in cervical cancer progression mediated by MMP-2 protein

  • T. Fernandes1
  • L.A. de Angelo-Andrade2
  • S.S. Morais3
  • G.A. Pinto3
  • C.A. Chagas1
  • S.S. Maria-Engler4
  • L.C. Zeferino1,*,

1Department of Obstetrics and Gynecology, Brazil

2Department of Pathology, Brazil

3Woman’s Hospital (CAISM), State University of Campinas, Brazil

4Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, Unicamp, Campinas, CP, Brazil

DOI: 10.12892/ejgo200804341 Vol.29,Issue 4,July 2008 pp.341-344

Published: 10 July 2008

*Corresponding Author(s): L.C. Zeferino E-mail: zeferino@hc.unicamp.br

Abstract

Metalloproteinases, especially metal loprotemase-2 (MMP-2), are known for their role in the degradation of the extracellular matrix. Nevertheless, a thorough understanding of MMP-2 expression in neoplastic lesions of the uterine cervix has yet to be accomplished. This study aimed to analyze the MMP-2 expression in cervical intraepithelial neoplasia III (CIN3) and in cervical squamous cell carcinoma, in tumor cells and adjacent stromal cells. MMP-2 expression was assessed by an immunohistochernical technique. MMP-2 expression was greater in the stromal cells of invasive carcinomas than in CIN3 (p < 0.0001). MMP-2 expression in stromal cells correlates with the clinical stage, gradually increasing as the tumor progresses (p = 0.04). This study corroborates that stromal cells play an important role in tumor invasion and progression, mediated by the progressive enhancement of MMP-2 expression from CIN3 to advanced invasive tumor. The intense MMP-2 expression most probably is associated with poor tumor prognosis.

Keywords

Matrix metalloproteinase 2; Cervix cancer; Cervical intraepithelial neoplasia; Stromal cells

Cite and Share

T. Fernandes,L.A. de Angelo-Andrade,S.S. Morais,G.A. Pinto,C.A. Chagas,S.S. Maria-Engler,L.C. Zeferino. Stromal cells play a role in cervical cancer progression mediated by MMP-2 protein. European Journal of Gynaecological Oncology. 2008. 29(4);341-344.

References

[1] International Agency for Research on Cancer. Cancer Epidemiolgy Databases. Globocan 2002 http://www-depdb.iarc.fr/globocan/ GLOBOframe.htm, 2007.

[2] Burd E.M.: “Human papillomavirus and cervical cancer”. Clin. Microbiol. Rev., 2003, 16, 1.

[3]Itoh Y., Nagase H.: “Matrix metalloproteinases in cancer”. Essays Biochem., 2002, 38, 21.

[4] Zhou C.Y., Yao J.F., Chen X.D.: “Expression of matrix metalloproteinase-2, 9 and their inhibitor-TIMP 1,2 in human squamous cell carcinoma of uterine cervix”. Ai Zheng, 2002, 2, 735.

[5]Benaud C., Dickson R.B., Thompson E.W.: “Roles of the matrix metalloproteinases in mammary gland development and cancer”. Breast Cancer Res. Treat., 1998, 50, 97.

[6] Baker A.H., Edwards D.R., Murphy G.: “Metalloproteinase inhibitors: biological actions and therapeutic opportunities”. J. Cell. Sci, 2002, 115, 3719.

[7] Brummer O., Bohmer G., Hollwitz B., Flemming P., Petry K.U., Kuhnle H.: “MMP-1 and MMP-2 in the cervix uteri in different steps of malignant transformation-an immunohistochemical study”. Gynecol. Oncol., 2002, 84, 222.

[8] Singer C.F., Kronsteiner N., Marton E., Kubista M., Cullen K.J., Hirtenlehner K. et al.: “MMP-2 and MMP-9 expression in breast cancer-derived human fibroblasts is differentially regulated by stromal-epithelial interactions”. Breast Cancer Res. Treat., 2002, 72, 69.

[9] Aznavoorian S., Murphy A.N., Stetler-Stevenson W.G., Liotta L.A.: “Molecular aspects of tumor cell invasion and metastasis”. Cancer, 1993, 71, 1368.

[10] Imai K., Ohuchi E., Aoki T., Nomura H., Fujii Y., Sato H. et al.: “Membrane-type matrix metalloproteinase 1 is a gelatinolytic enzyme and is secreted in a complex with tissue inhibitor of metalloproteinase 2”. Cancer Res., 1996, 56, 2707.

[11] van der Jagt M.F., Sweep F.C., Waas E.T., Hendriks T., Ruers T.J., Merry A.H.: “Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer”. Cancer Lett., 2006, 237, 289.

[12] Masui T., Doi R., Koshiba T., Fujimoto K., Tsuji S., Nakajima S., et al.: “RECK expression in pancreatic cancer: its correlation with lower invasiveness and better prognosis”. Clin. Cancer Res., 2003, 9, 1779.

[13] Boag A.H., Young I.D.: “Increased expression of the 72-kd type IV collagenase in prostatic adenocarcinoma. Demonstration by immunohistochemistry and in situ hybridization”. Am. J. Pathol., 1994, 144, 585.

[14] Davies B., Waxman J., Wasan H., Abel P., Williams G., Krausz T., et al.: “Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion”. Cancer Res., 1993, 53, 5365.

[15] Pellikainen J.M., Ropponen K.M., Kataja V.V., Kellokoski J.K., Eskelinen M.J., Kosma V.M.: “Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER-2, and prognosis”. Clin. Cancer Res., 2004, 10, 7621.

[16] Gaiotto M.A., Focchi J., Ribalta J., Stávale J.N., Baracat E.C., Lima G.R. et al.: “Comparative study of MMP-2 immune expression in normal uterine cervix, intraepithelial neoplasias, and squamous cells cervical carcinoma”. Am. J. Obstet. Gynecol., 2004, 190, 1278.

[17] Branca M., Ciotti M., Giorgi C., Santini D., Di Bonito L., Costa S. et al.: “Matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2) are prognostic factors in cervical cancer, related to invasive disease but to high-risk human papillomavirus (HPV) or virus persistence after treatment of CIN”. Anticancer Res., 2006, 26, 1543.

[18] Davidson B., Goldberg I., Kopolovic J., Lener-Geva L., Gotlieb W.H., Ben-Baruch G. et al.: “MMP-2 and TIMP-2 expression correlates with poor prognosis in cervical carcinoma - a clinicopathologic study using immunohistochemistry and mRNA in situ hybridization”. Gynecol. Oncol., 1999, 73, 372.

[19] Ishikawa S., Takenaka K., Yanagihara K., Miyahara R., Kawano Y., Otake Y. et al.: “Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell-lung cancer”. Clin. Cancer Res., 2004, 10, 6579.

[20] Masaki T., Matsuoka H., Sugiyama M., Abe N., Izumisato Y., Goto A. et al.: “Laminin-5 gamma 2 chain and matrix metalloproteinase-2 may trigger colorectal carcinoma invasiveness through formation of budding tumor cells”. Anticancer Res., 2003, 23, 4113.

[21] Sun J., Hemler M.E.: “Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions”. Cancer Res., 2001, 61, 2276.

[22] Sier C.F., Zuidwijk K., Zijlmans H.J., Hanemaaijer R., Mulder-Stapel A.A., Prins F.A. et al.: “EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma”. Int. J. Cancer, 2006, 118, 2991.

[23] Smola-Hess S., Pahne J., Mauch C., Zigrino P., Smola H., Pfister H.: “Expression of membrane type 1 matrix metalloproteinase in papillomavirus-positive cell: role of the human papillomavirus (HPV) 16 and HPV8 E7 gene products”. J. Gen. Virol., 2005, 86, 1291.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top