Presence of Myofibroblasts and Expression of Matrix Metalloproteinase-2 (MMP-2) in Ameloblastomas Correlate with Rupture of the Osseous Cortical

Eduardo Rodrigues Fregnani; Lays M. Sobral; Fabio Abreu Alves; Fernando Augusto Soares; Luis Paulo Kowalski; Ricardo D. Coletta

doi:10.1007/s12253-008-9110-4

Pathology & Oncology Research

June 2009, Volume 15, Issue 2, pp 231–240

Presence of Myofibroblasts and Expression of Matrix Metalloproteinase-2 (MMP-2) in Ameloblastomas Correlate with Rupture of the Osseous Cortical

Authors
Authors and affiliations

Eduardo Rodrigues FregnaniEmail author
Lays M. Sobral
Fabio Abreu Alves
Fernando Augusto Soares
Luis Paulo Kowalski
Ricardo D. Coletta

Original Paper

First Online:: 19 December 2008

Received:: 01 June 2008
Accepted:: 07 October 2008

DOI: 10.1007/s12253-008-9110-4

Cite this article as:: Fregnani, E.R., Sobral, L.M., Alves, F.A. et al. Pathol. Oncol. Res. (2009) 15: 231. doi:10.1007/s12253-008-9110-4

19 Citations
161 Downloads

Abstract

Myofibroblasts are frequent in the stroma of neoplasm and by the expression of proteinases they can influence tumor infiltration and progression. In the present study, presence of myofibroblasts and expression of matrix metalloproteinase-2 (MMP-2) and urokinase plasminogen activator (uPA) were examined in intra-osseous solid multicystic ameloblastomas to determine their roles in the clinicopathological features of the tumors. Fifty seven ameloblastomas were analyzed immunohistochemically with antibodies against the isoform α of the smooth muscle actin (α-SMA), a specific marker of myofibroblasts, MMP-2 and uPA. Myofibroblasts were found in the stroma, in close contact with neoplastic cell islands, of ~58% (n = 33) of the ameloblastomas. MMP-2 and uPA were found in the cytoplasm of both neoplastic and stromal cells. A significant correlation between presence of myofibroblasts and MMP-2 expression was observed. Abundant presence of myofibroblast in the stroma of the tumors and expression of MMP-2 in the neoplastic or stromal cells were significantly correlated with rupture of the osseous cortical, which has been considered an important prognostic marker of ameloblastoma aggressiveness. Ours results suggest that abundant presence of myofibroblasts and expression of MMP-2 in solid ameloblastomas may be associated with a more aggressive infiltrative behavior.

Keywords

Ameloblastoma Matrix metalloproteinase-2 Myofibroblast Prognosis Urokinase plasminogen activator

Supplementary material

12253_2008_9110_MOESM1_ESM.doc (35 kb)

TableCorrelation of the bone cortical status and duration of the symptoms or tumor size in ameloblastomas (DOC 35.0 KB).

References

1.
Desmouliere A, Chaponnier C, Gabbiani G (2005) Tissue repair, contraction, and the myofibroblast. Wound Repair Regen 13:7–12PubMedCrossRefGoogle Scholar
2.
Desmouliere A, Guyot C, Gabbiani G (2004) The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int J Dev Biol 48:509–517PubMedCrossRefGoogle Scholar
3.
Kuroda N, Shimasaki N, Miyazaki E et al. (2006) The distribution of myofibroblasts and CD34-positive stromal cells in normal renal pelvis and ureter and their cancers. Histol Histopathol 21:1303–1307PubMedGoogle Scholar
4.
Powell DW, Adegboyega PA, Di Mari JF et al. (2005) Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer. Am J Physiol Gastrointest Liver Physiol 289:G2–G7PubMedCrossRefGoogle Scholar
5.
Darby IA, Hewitson TD (2007) Fibroblast differentiation in wound healing and fibrosis. Int Rev Cytol 257:143–179PubMedCrossRefGoogle Scholar
6.
Bitu CC, Sobral LM, Kellermann MG et al. (2006) Heterogeneous presence of myofibroblasts in hereditary gingival fibromatosis. J Clin Periodontol 33:393–400PubMedCrossRefGoogle Scholar
7.
Gabbiani G (2003) The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 200:500–503PubMedCrossRefGoogle Scholar
8.
Kunz-Schughart LA, Knuechel R (2002) Tumor-associated fibroblasts (part II): Functional impact on tumor tissue. Histol Histopathol 17:623–637PubMedGoogle Scholar
9.
Kunz-Schughart LA, Knuechel R (2002) Tumor-associated fibroblasts (part I): Active stromal participants in tumor development and progression? Histol Histopathol 17:599–621PubMedGoogle Scholar
10.
Scotton CJ, Chambers RC (2007) Molecular targets in pulmonary fibrosis: the myofibroblast in focus. Chest 132:1311–1321PubMedCrossRefGoogle Scholar
11.
Mukaratirwa S, Koninkx JF, Gruys E et al. (2005) Mutual paracrine effects of colorectal tumour cells and stromal cells: modulation of tumour and stromal cell differentiation and extracellular matrix component production in culture. Int J Exp Pathol 86:219–229PubMedCrossRefGoogle Scholar
12.
Offersen BV, Nielsen BS, Hoyer-Hansen G et al. (2003) The myofibroblast is the predominant plasminogen activator inhibitor-1-expressing cell type in human breast carcinomas. Am J Pathol 163:1887–1899PubMedGoogle Scholar
13.
Orimo A, Weinberg RA (2006) Stromal fibroblasts in cancer: a novel tumor-promoting cell type. Cell Cycle 5:1597–1601PubMedGoogle Scholar
14.
Helary C, Ovtracht L, Coulomb B et al. (2006) Dense fibrillar collagen matrices: a model to study myofibroblast behaviour during wound healing. Biomaterials 27:4443–4452PubMedCrossRefGoogle Scholar
15.
Soini Y, Satta J, Maatta M et al. (2001) Expression of MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA in valvular lesions of the heart. J Pathol 194:225–231PubMedCrossRefGoogle Scholar
16.
Pender SL, MacDonald TT (2004) Matrix metalloproteinases and the gut - new roles for old enzymes. Curr Opin Pharmacol 4:546–550PubMedCrossRefGoogle Scholar
17.
Hatane T, Yoshida E, Kawano J et al. (1998) Prostaglandin I2 analog enhances the expression of urokinase-type plasminogen activator and wound healing in cultured human fibroblast. Biochim Biophys Acta 1403:189–198PubMedCrossRefGoogle Scholar
18.
Dubuisson L, Monvoisin A, Nielsen BS et al. (2000) Expression and cellular localization of the urokinase-type plasminogen activator and its receptor in human hepatocellular carcinoma. J Pathol 190:190–195PubMedCrossRefGoogle Scholar
19.
Monvoisin A, Neaud V, De Ledinghen V et al. (1999) Direct evidence that hepatocyte growth factor-induced invasion of hepatocellular carcinoma cells is mediated by urokinase. J Hepatol 30:511–518PubMedCrossRefGoogle Scholar
20.
Plekhanova OS, Stepanova VV, Ratner EI (2006) Urokinase plasminogen activator in injured adventitia increases the number of myofibroblasts and augments early proliferation. J Vasc Res 43:437–446PubMedCrossRefGoogle Scholar
21.
Reichart PA, Philipsen HP, Sonner S (1995) Ameloblastoma: biological profile of 3677 cases. Eur J Cancer B Oral Oncol 31B:86–99PubMedCrossRefGoogle Scholar
22.
Kumamoto H, Ooya K (2006) Immunohistochemical detection of MT1-MMP, RECK, and EMMPRIN in ameloblastic tumors. J Oral Pathol Med 35:345–351PubMedCrossRefGoogle Scholar
23.
Kumamoto H, Ooya K (2007) Immunohistochemical detection of uPA, uPAR, PAI-1, and maspin in ameloblastic tumors. J Oral Pathol Med 36:488–494PubMedGoogle Scholar
24.
Kumamoto H, Yamauchi K, Yoshida M et al. (2003) Immunohistochemical detection of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in ameloblastomas. J Oral Pathol Med 32:114–120PubMedCrossRefGoogle Scholar
25.
Pinheiro JJ, Freitas VM, Moretti AI et al (2004) Local invasiveness of ameloblastoma. Role played by matrix metalloproteinases and proliferative activity. Histopathology 45:65–72PubMedCrossRefGoogle Scholar
26.
Suh KS, Crutchley JM, Koochek A et al. (2007) Reciprocal modifications of CLIC4 in tumor epithelium and stroma mark malignant progression of multiple human cancers. Clin Cancer Res 13:121–131PubMedCrossRefGoogle Scholar
27.
Kellermann MG, Sobral LM, da Silva SD, Zecchin KG, Graner E, Lopes MA, Kowalski LP, Coletta RD (2008) Mutual paracrine effects of oral squamous cell carcinoma cells and normal oral fibroblasts: induction of fibroblast to myofibroblast transdifferentiation and modulation of tumor cell proliferation. Oral Oncol 4:509–517CrossRefGoogle Scholar
28.
Mahadevan D, Von Hoff DD (2007) Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther 6:1186–1197PubMedCrossRefGoogle Scholar
29.
Casey TM, Eneman J, Crocker A et al (2007) Cancer associated fibroblasts stimulated by transforming growth factor beta1 (TGF-beta1) increase invasion rate of tumor cells: a population study. Breast Cancer Res Treat Aug 3. doi:10.1007/s10549-007-9684-7
30.
Kellermann MG, Sobral LM, da Silva SD et al. (2007) Myofibroblasts in the stroma of oral squamous cell carcinoma are associated with poor prognosis. Histopathology 51:849–853PubMedCrossRefGoogle Scholar
31.
Lewis MP, Lygoe KA, Nystrom ML et al. (2004) Tumour-derived TGF-beta1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells. Br J Cancer 90:822–832PubMedCrossRefGoogle Scholar
32.
Chauhan H, Abraham A, Phillips JR et al. (2003) There is more than one kind of myofibroblast: analysis of CD34 expression in benign, in situ, and invasive breast lesions. J Clin Pathol 56:271–276PubMedCrossRefGoogle Scholar
33.
Shimasaki N, Kuroda N, Miyazaki E et al. (2006) The distribution pattern of myofibroblasts in the stroma of human bladder carcinoma depends on their invasiveness. Histol Histopathol 21:349–353PubMedGoogle Scholar
34.
Takata T, Miyauchi M, Ogawa I et al. (2000) Immunoexpression of transforming growth factor beta in desmoplastic ameloblastoma. Virchows Arch 436:319–323PubMedCrossRefGoogle Scholar
35.
Smith SM, Bartov SA (1986) Ameloblastoma with myofibroblasts: first report. J Oral Pathol 15:284–286PubMedCrossRefGoogle Scholar
36.
Rothouse LS, Majack RA, Fay JT (1980) An ameloblastoma with myofibroblasts and intracellular septate junctions. Cancer 45:2858–2863PubMedCrossRefGoogle Scholar
37.
Lombardi T, Morgan PR (1995) Immunohistochemical characterisation of odontogenic cysts with mesenchymal and myofilament markers. J Oral Pathol Med 24:170–176PubMedCrossRefGoogle Scholar
38.
Vered M, Shohat I, Buchner A et al. (2005) Myofibroblasts in stroma of odontogenic cysts and tumors can contribute to variations in the biological behavior of lesions. Oral Oncol 41:1028–1033PubMedCrossRefGoogle Scholar
39.
Carlson ER, Marx RE (2006) The ameloblastoma: primary, curative surgical management. J Oral Maxillofac Surg 64:484–494PubMedCrossRefGoogle Scholar
40.
Ueno S, Mushimoto K, Shirasu R (1989) Prognostic evaluation of ameloblastoma based on histologic and radiographic typing. J Oral Maxillofac Surg 47:11–15PubMedCrossRefGoogle Scholar
41.
Sampson DE, Pogrel MA (1999) Management of mandibular ameloblastoma: the clinical basis for a treatment algorithm. J Oral Maxillofac Surg 57:1074–1077; discussion 78–9PubMedCrossRefGoogle Scholar
42.
McKaig BC, McWilliams D, Watson SA et al. (2003) Expression and regulation of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases by intestinal myofibroblasts in inflammatory bowel disease. Am J Pathol 162:1355–1360PubMedGoogle Scholar
43.
Czochra P, Klopcic B, Meyer E et al. (2006) Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice. J Hepatol 45:419–428PubMedCrossRefGoogle Scholar
44.
Seomun Y, Kim J, Lee EH et al. (2001) Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells. Biochem J 358:41–48PubMedCrossRefGoogle Scholar
45.
Porter KE, Turner NA, O’Regan DJ et al. (2004) Tumor necrosis factor alpha induces human atrial myofibroblast proliferation, invasion and MMP-9 secretion: inhibition by simvastatin. Cardiovasc Res 64:507–515PubMedCrossRefGoogle Scholar
46.
Deng X, He G, Levine A et al. (2008) Adenovirus-mediated expression of TIMP-1 and TIMP-2 in bone inhibits osteolytic degradation by human prostate cancer. Int J Cancer 122:209–218PubMedCrossRefGoogle Scholar
47.
Dass K, Ahmad A, Azmi AS et al. (2008) Evolving role of uPA/uPAR system in human cancers. Cancer Treat Rev 34:122–136PubMedCrossRefGoogle Scholar
48.
Fisher JL, Mackie PS, Howard ML et al. (2001) The expression of the urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model. Clin Cancer Res 7:1654–1660PubMedGoogle Scholar
49.
Stillfried GE, Saunders DN, Ranson M (2007) Plasminogen binding and activation at the breast cancer cell surface: the integral role of urokinase activity. Breast Cancer Res 9:R14PubMedCrossRefGoogle Scholar
50.
Nielsen BS, Rank F, Illemann M et al. (2007) Stromal cells associated with early invasive foci in human mammary ductal carcinoma in situ coexpress urokinase and urokinase receptor. Int J Cancer 120:2086–2095PubMedCrossRefGoogle Scholar
51.
Ji F, Chen YL, Jin EY et al. (2005) Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer. World J Gastroenterol 11:3222–3226PubMedGoogle Scholar
52.
Bernstein AM, Twining SS, Warejcka DJ et al. (2007) Urokinase receptor cleavage: a crucial step in fibroblast-to-myofibroblast differentiation. Mol Biol Cell 18:2716–2727PubMedCrossRefGoogle Scholar

Copyright information

Authors and Affiliations

Eduardo Rodrigues Fregnani
- 1
Email author
Lays M. Sobral
- 2
Fabio Abreu Alves
- 1
Fernando Augusto Soares
- 3
Luis Paulo Kowalski
- 4
Ricardo D. Coletta
- 2

1.Department of StomatologyA. C. Camargo Cancer HospitalSão PauloBrazil
2.Department of Oral DiagnosisSchool of Dentistry, State University of CampinasPiracicabaBrazil
3.Department of PathologyA. C. Camargo Cancer HospitalSão PauloBrazil
4.Department of Head and Neck Surgery and OtorhinolaryngologyA.C. Camargo Cancer HospitalSão PauloBrazil

Personalised recommendations

Article actions

Unlimited access to the full article
Instant download
Include local sales tax if applicable

Subscribe to Journal

Get Access to

Pathology & Oncology Research

for the whole of 2017

Presence of Myofibroblasts and Expression of Matrix Metalloproteinase-2 (MMP-2) in Ameloblastomas Correlate with Rupture of the Osseous Cortical

Abstract

Keywords

Supplementary material

Copyright information

Authors and Affiliations

Personalised recommendations

Cookies