Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Ophthalmology
Published in: BMC Ophthalmology 1/2016

Open Access 01-12-2016 | Research article

CD147 and matrix-metalloproteinase-2 expression in metastatic and non-metastatic uveal melanomas

Authors: Julia Lüke, Vlatka Vukoja, Tim Brandenbusch, Khaled Nassar, Jens Martin Rohrbach, Salvatore Grisanti, Matthias Lüke, Aysegül Tura

Published in: BMC Ophthalmology | Issue 1/2016

Login to get access

Abstract

Background

Extracellular matrix remodelling regulated by matrix-metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis.

Methods

The expression of CD147 and MMP-2 was analyzed in 49 samples of uveal melanomas. Triple immunofluorescence stainings using markers against glial cells (GFAP), endothelial cells (CD34) and macrophages (CD68) were performed to further analyse the exact localisation of CD147 and MMP-2 positivity. In 28 cases clinical metastatic disease were found. The remaining 21 cases showed no signs of metastatic disease for an average follow-up of 10 years. Correlation analysis (Pearson correlation) was performed to analyse the association of CD147 and MMP-2 expression with known prognostic factors, vasculogenic mimicry (VM), the mature vasculature (von Willebrand Factor) and tumor induced angiogenesis (by means of Endoglin expression).

Results

CD147 and MMP-2 were expressed in 47 (96.0 %) of the uveal melanomas. CD147 up-regulation was significantly correlated with a higher MMP-2 expression. The overall expression analysis revealed no significant difference in the metastatic (p = 0.777) and non-metastatic subgroup (p = 0.585). No correlation of CD147 expression and any system of blood supply was evident. In the non-metastatic sub-group a significant correlation of clustered CD147 positive cells with largest basal diameter (p = 0.039), height (p = 0.047) and TNM-stage (p = 0.013) was evident.

Conclusions

These data may indicate that CD147 regulates MMP-2 expression in uveal melanoma cells.
Literature
1.
Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol. 1999;155:739–52.CrossRefPubMedPubMedCentral
2.
Moses MA. The regulation of neovascularization of matrix metalloproteinases and their inhibitors. Stem Cells. 1997;15:180–9.CrossRefPubMed
3.
Nelson AR, Fingleton B, Rothenberg ML, et al. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol. 2000;18:1135–49.PubMed
4.
Bergers G, Brekken R, McMahon G, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000;2:737–44.CrossRefPubMedPubMedCentral
5.
Fang J, Shing Y, Wiederschain D, et al. Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. Proc Natl Acad Sci U S A. 2000;97:3884–9.CrossRefPubMedPubMedCentral
6.
Biswas C, Zhang Y, DeCastro R, et al. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995;55:434–9.PubMed
7.
Huet E, Gabison EE, Mourah S, et al. Role of emmprin/CD147 in tissue remodeling. Connect Tissue Res. 2008;49:175–9.CrossRefPubMed
8.
Muramatsu T, Miyauchi T. Basigin (CD147): a multifunctional transmembrane protein involved in reproduction, neural function, inflammation and tumor invasion. Histol Histopathol. 2003;18:981–7.PubMed
9.
Nabeshima K, Iwasaki H, Koga K, et al. Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression. Pathol Int. 2006;56:359–67.CrossRefPubMed
10.
Yan L, Zucker S, Toole BP. Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression. Thromb Haemost. 2005;93:199–204.PubMed
11.
Määttä M, Tervahartiala T, Kaarniranta K, et al. Immunolocalization of EMMPRIN (CD147) in the human eye and detection of soluble form of EMMPRIN in ocular fluids. Curr Eye Res. 2006;31:917–24.CrossRefPubMed
12.
Seppälä HP, Määttä M, Rautia M, et al. EMMPRIN and MMP-1 in keratoconus. Cornea. 2006;25:325–30.CrossRefPubMed
13.
Gabison EE, Mourah S, Steinfels E, et al. Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epithelio-stromal interactions and matrix metalloproteinase induction. Am J Pathol. 2005;166:209–19.CrossRefPubMedPubMedCentral
14.
Chen X, Lin J, Kanekura T, et al. A small interfering CD147-targeting RNA inhibited the proliferation, invasiveness, and metastatic activity of malignant melanoma. Cancer Res. 2006;66:11323–30.CrossRefPubMed
15.
Kanekura T, Chen X, Kanzaki T. Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. Int J Cancer. 2002;99:520–8.CrossRefPubMed
16.
17.
Folberg R, Pe’er J, Gruman LM, et al. The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case–control study. Hum Pathol. 1992;23:1298–305.CrossRefPubMed
18.
Stenzel M, Tura A, Nassar K, Rohrbach JM, Grisanti S, Lüke M, Lüke J. Analysis of Caveolin-1 and Phosphoinositol-3 Kinase expression in primary uveal melanomas. Clin Experiment Ophthalmol. Epub 2015 Nov 21. doi:10.​1111/​ceo.​12686
19.
Kivela T. Immunohistochemical staining followed by bleaching of melanin: a practical method for ophthalmic pathology. Br J Biomed Sci. 1995;52:325–6.PubMed
20.
Kanekura T, Chen X. CD147/basigin promotes progression of malignant melanoma and other cancers. J Dermatol Sci. 2010;57:149–54.CrossRefPubMed
21.
van den Oord JJ, Paemen L, Opdenakker G, et al. Expression of gelatinase B and the extracellular matrix metalloproteinase inducer EMMPRIN in benign and malignant pigment cell lesions of the skin. Am J Pathol. 1997;151:665–70.PubMedPubMedCentral
22.
Real FX, Houghton AN, Albino AP, et al. Surface antigens of melanomas and melanocytes defined by mouse monoclonal antibodies: specificity analysis and comparison of antigen expression in cultured cells and tissues. Cancer Res. 1985;45:4401–11.PubMed
23.
24.
Zhang C, Man DP, Ma SM, et al. Expressions and significances of CD147, OPN and MMP-2 in oral squamous cell carcinoma. Sichuan Da Xue Xue Bao Yi Xue Ban. 2012;43:683–6.PubMed
25.
26.
Xiong L, Edwards 3rd CK, Zhou L. The biological function and clinical utilization of CD147 in human diseases: a review of the current scientificliterature. Int J Mol Sci. 2014;15(10):17411–41.CrossRefPubMedPubMedCentral
27.
Yang M, Yuan Y, Zhang H, et al. Prognostic significance of CD147 in patients with glioblastoma. J Neurooncol. 2013;115:19–26.CrossRefPubMed
28.
Wysocki PJ. Targeted therapy of hepatocellular cancer. Expert Opin Investig Drugs. 2010;19:265–74.CrossRefPubMed
29.
Xu J, Xu HY, Zhang Q, et al. HAb18G/CD147 functions in invasion and metastasis of hepatocellular carcinoma. Mol Cancer Res. 2007;5:605–14.CrossRefPubMed
30.
Li HY, Cao LM. Inhibitory effect of arsenic trioxide on invasion in human hepatocellular carcinoma SMMC-7721 cells and its mechanism. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2012;28:1254–7.CrossRefPubMed
31.
Millimaggi D, Mari M, DA S, et al. Vasculogenic mimicry of human ovarian cancer cells: role of CD147. Int J Oncol. 2009;35:1423–8.PubMed
32.
Duffy MJ, McGowan PM, Gallagher WM. Cancer invasion and metastasis: changing views. J Pathol. 2008;214:283–93.CrossRefPubMed
33.
Chang CW, Hsieh YH, Yang WE, et al. Epigallocatechingallate inhibits migration of human uveal melanoma cells via down-regulation of matrixmetalloproteinase-2 activity and ERK1/2 pathway. Biomed Res Int. 2014;2014:141582.PubMedPubMedCentral
34.
Planagumà J, Liljeström M, Alameda F, et al. Matrix metalloproteinase-2 and matrix metalloproteinase-9 codistribute with transcription factors RUNX1/AML1 and ETV5/ERM at the invasive front of endometrial and ovarian carcinoma. Hum Pathol. 2011;42:57–67.CrossRefPubMed
35.
Milia-Argeiti E, Huet E, Labropoulou VT, Mourah S, Fenichel P, Karamanos NK, Menashi S, Theocharis AD. Imbalance of MMP-2 and MMP-9 expression versus TIMP-1 and TIMP-2 reflects increased invasiveness of human testicular germ cell tumours. Int J Androl. 2012;35(6):835–44.CrossRefPubMed
36.
Hong SW, Kang YK, Lee B, Lee WY, Jang YG, Paik IW, Lee H. Matrix metalloproteinase-2 and −7 expression in colorectal cancer. J Korean Soc Coloproctol. 2011;27:133–9.CrossRefPubMedPubMedCentral
37.
Chen Y, Wang X, Chen G, Dong C, Zhang D. The impact of matrix metalloproteinase 2 on prognosis and clinicopathology of breast cancerpatients: a systematic meta-analysis. PLoS One. 2015;27(10):e0121404.CrossRef
38.
Qian Q, Wang Q, Zhan P, et al. The role of matrix metalloproteinase 2 on the survival of patients with non-small cell lung cancer: a systematic review with meta-analysis. Cancer Invest. 2010;28:661–9.CrossRefPubMed
39.
Terada T, Okada Y, Nakanuma Y. Expression of immunoreactive matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human normal livers and primary liver tumors. Hepatology. 1996;23:1341–4.CrossRefPubMed
40.
de Oliveira PF, de Carvalho Fraga CA, Gomes ES, et al. Protein expression of MMP-2 and MT1-MMP in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma. Int J Surg Pathol. 2015;23:20–5.CrossRef
41.
Xie T, Dong B, Yan Y, Hu G, Xu Y. Association between MMP-2 expression and prostate cancer: A meta-analysis. Biomed Rep. 2016;4:241–5.PubMedPubMedCentral
42.
Liu C. Pathological and prognostic significance of matrix metalloproteinase-2 expression in ovarian cancer: a meta-analysis. Clin Exp Med. 2015. Epub ahead of print.
43.
Cottam DW, Rennie IG, Woods K, Parsons MA, Bunning RA, Rees RC. Gelatinolytic metalloproteinase secretion patterns in ocular melanoma. Invest Ophthalmol Vis Sci. 1992;33:1923–7.PubMed
44.
Bérubé M, Deschambeault A, Boucher M, Germain L, Petitclerc E, Guérin SL. MMP-2 expression in uveal melanoma: differential activation status dictated by the cellular environment. Mol Vis. 2005;11:1101–11.PubMed
45.
Väisänen A, Kallioinen M, von Dickhoff K, et al. Matrix metalloproteinase-2 (MMP-2) immunoreactive protein--a new prognostic marker in uveal melanoma? J Pathol. 1999;188:56–62.CrossRefPubMed
46.
Bougatef F, Menashi S, Khayati F, et al. EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2. PLoS One. 2010;5:e12265.CrossRefPubMedPubMedCentral
47.
Bougatef F, Quemener C, Kellouche S, et al. EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2alpha-mediated regulation of soluble VEGF isoforms and their receptor VEGFR-2. Blood. 2009;114:5547–56.CrossRefPubMed
48.
Desch A, Strozyk EA, Bauer AT, et al. Highly invasive melanoma cells activate the vascular endothelium via an MMP-2/integrin alphavbeta5-induced secretion of VEGF-A. Am J Pathol. 2012;181:693–705.CrossRefPubMed
49.
Chen L, Zhang S, Li X, et al. A pilot study of vasculogenic mimicry immunohistochemical expression in intraocular melanoma model. Oncol Rep. 2009;21:989–94.CrossRefPubMed
50.
Wang X, Xu G, Fan J, et al. Mechanical stretching induces matrix metalloproteinase-2 expression in rat retinal glial (Müller) cells. Neuroreport. 2013;24:224–8.CrossRefPubMed
51.
Hou X, Han QH, Hu D, et al. Mechanical force enhances MMP-2 activation via p38 signaling pathway in human retinal pigment epithelial cells. Graefes Arch Clin Exp Ophthalmol. 2009;247:1477–86.CrossRefPubMed
52.
Kowluru RA, Kanwar M. Oxidative stress and the development of diabetic retinopathy: contributory role of matrix metalloproteinase-2. Free Radic Biol Med. 2009;46:1677–85.CrossRefPubMedPubMedCentral
53.
Zhang X, Sakamoto T, Hata Y, et al. Expression of matrix metalloproteinases and their inhibitors in experimental retinal ischemia-reperfusion injury in rats. Exp Eye Res. 2002;74:577–7784.CrossRefPubMed
Metadata
Title
CD147 and matrix-metalloproteinase-2 expression in metastatic and non-metastatic uveal melanomas
Authors
Julia Lüke
Vlatka Vukoja
Tim Brandenbusch
Khaled Nassar
Jens Martin Rohrbach
Salvatore Grisanti
Matthias Lüke
Aysegül Tura
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2016
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-016-0222-4

Other articles of this Issue 1/2016

BMC Ophthalmology 1/2016 Go to the issue

Research article

Retinal pigment epithelial atrophy over polypoidal choroidal vasculopathy lesions during ranibizumab monotherapy

Research article

Outcome of 2 cc pure sulfur hexafluoride gas tamponade for macular hole surgery

Case report

Inhibition of recurrence of epithelial ingrowth with an amniotic membrane pressure patch to a laser in situ keratomileusis flap with a central stellate laceration: a case report

Case report

Case report: Aqueous and Vitreous amino-acid concentrations in a patient with maple syrup urine disease operated on rhegmatogenous retinal detachment

Research article

CpG site methylation in CRYAA promoter affect transcription factor Sp1 binding in human lens epithelial cells

Research article

T-helper-associated cytokines expression by peripheral blood mononuclear cells in patients with polypoidal choroidal vasculopathy and age-related macular degeneration