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World Journal of Surgical Oncology
Published in: World Journal of Surgical Oncology 1/2011

Open Access 01-12-2011 | Research

Microvessel density and heparanase over-expression in clear cell renal cell cancer: correlations and prognostic significances

Authors: Juchao Ren, Hainan Liu, Lei Yan, Sujian Tian, Dawei Li, Zhonghua Xu

Published in: World Journal of Surgical Oncology | Issue 1/2011

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Abstract

Background

Tumor angiogenesis is important in the progression of malignancies, and heparanase plays an important role in sustaining the pathology of clear cell renal cell cancer (ccRCC). The study was carried out to investigate the correlations between microvessel density (MVD) and heparanase expression containing prognostic significances in the patients with ccRCC.

Methods

Specimens from 128 patients with ccRCC were investigated by immunohistochemistry for MVD. RT-PCR and immunohistochemistry were used to detect heparanase expression. Correlations between MVD, heparanase expression, and various clinico-pathological factors were studied. The prognostic significances of MVD and heparanase expression were also analysed.

Results

We discovered a statistically significant prevalence of higher MVD in ccRCC compared with adjacent normal renal tissues. MVD was positively correlated with TNM stage and distant metastasis in ccRCC patients, and was also correlated with the expression level of heparanase.
Heparanase is over-expressed and correlated with TNM stage, histologic grade, distant metastasis and lymphatic metastasis in ccRCC. High MVD and heparanase over-expression inversely correlate with the survival of ccRCC patients.

Conclusions

Heparanase contributes to angiogenesis of ccRCC and over-expression of heparanase is an independent predictors of prognosis for ccRCC. MVD is correlated with tumor development and metastasis in ccRCC.
Appendix
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Literature
1.
Eble JN, Sauter G, Epstein JI, Sesterhenn IA: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. 2004, Lyon: IARCPress
2.
3.
Czekierdowski A, Czekierdowska S, Czuba B, Cnota W, Sodowski K, Kotarski J, Zwirska- Korczala K: Microvessel density assessment in benign and malignant endometrial changes. J Physiol Pharmacol. 2008, 59 (Suppl 4): 45-51.PubMed
4.
Thelen A, Scholz A, Benckert C, Schroder M, Weichert W, Wiedenmann B, Neuhaus P, Jonas S: Microvessel density correlates with lymph node metastases and prognosis in hilar cholangiocarcinoma. J Gastroenterol. 2008, 43: 959-966.CrossRefPubMed
5.
Svagzdys S, Lesauskaite V, Pavalkis D, Nedzelskiene I, Pranys D, Tamelis A: Microvessel density as new prognostic marker after radiotherapy in rectal cancer. BMC Cancer. 2009, 9: 95-PubMedCentralCrossRefPubMed
6.
7.
Yurchenco PD, Schittny JC: Molecular architecture of basement membranes. FASEB J. 1990, 4: 1577-1590.PubMed
8.
Ferro V, Hammond E, Fairweather JK: The development of inhibitors of heparanase, a key enzyme involved in tumour metastasis, angiogenesis and inflammation. Mini Rev Med Chem. 2004, 4: 693-702.CrossRefPubMed
9.
Tang W, Nakamura Y, Tsujimoto M, Sato M, Wang X, Kurozumi K, Nakahara M, Nakao K, Nakamura M, Mori I, Kakudo K: Heparanase: a key enzyme in invasion and metastasis of gastric carcinoma. Mod Pathol. 2002, 15: 593-598.CrossRefPubMed
10.
Koliopanos A, Friess H, Kleeff J, Shi X, Liao Q, Pecker I, Vlodavsky I, Zimmermann A, Buchler MW: Heparanase expression in primary and metastatic pancreatic cancer. Cancer Res. 2001, 61: 4655-4659.PubMed
11.
Shinyo Y, Kodama J, Hongo A, Yoshinouchi M, Hiramatsu Y: Heparanase expression is an independent prognostic factor in patients with invasive cervical cancer. Ann Oncol. 2003, 14: 1505-1510.CrossRefPubMed
12.
Friedmann Y, Vlodavsky I, Aingorn H, Aviv A, Peretz T, Pecker I, Pappo O: Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis. Am J Pathol. 2000, 157: 1167-1175.PubMedCentralCrossRefPubMed
13.
Gohji K, Hirano H, Okamoto M, Kitazawa S, Toyoshima M, Dong J, Katsuoka Y, Nakajima M: Expression of three extracellular matrix degradative enzymes in bladder cancer. Int J Cancer. 2001, 95: 295-301.CrossRefPubMed
14.
Lerner I, Baraz L, Pikarsky E, Meirovitz A, Edovitsky E, Peretz T, Vlodavsky I, Elkin M: Function of heparanase in prostate tumorigenesis: potential for therapy. Clin Cancer Res. 2008, 14: 668-676.CrossRefPubMed
15.
Hermanek P, Seib H, Wittekind C: Clinical significance and current status. Pathologe. 1997, 18: 153-159.CrossRefPubMed
16.
Fuhrman SA, Lasky LC, Limas C: Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982, 6: 655-663.CrossRefPubMed
17.
Zetser A, Levy-Adam F, Kaplan V, Gingis-Velitski S, Bashenko Y, Schubert S, Flugelman MY, Vlodavsky I, Ilan N: Processing and activation of latent heparanase occurs in lysosomes. J Cell Sci. 2004, 117: 2249-2258.CrossRefPubMed
18.
Doweck I, Kaplan-Cohen V, Naroditsky I, Sabo E, Ilan N, Vlodavsky I: Heparanase localization and expression by head and neck cancer: correlation with tumor progression and patient survival. Neoplasia. 2006, 8: 1055-1061.PubMedCentralCrossRefPubMed
19.
Zubac DP, Bostad L, Kihl B, Seidal T, Wentzel-Larsen T, Haukaas SA: The expression of thrombospondin-1 and p53 in clear cell renal cell carcinoma: its relationship to angiogenesis, cell proliferation and cancer specific survival. J Urol. 2009, 182: 2144-2149.CrossRefPubMed
20.
Bai RJ, Cheng XG, Qu H, Shen BZ, Han MJ, Wu ZH: Solitary pulmonary nodules: comparison of multi-slice computed tomography perfusion study with vascular endothelial growth factor and microvessel density. Chin Med J (Engl). 2009, 122: 541-547.
21.
Ben-Izhak O, Kaplan-Cohen V, Ilan N, Gan S, Vlodavsky I, Nagler R: Heparanase expression in malignant salivary gland tumors inversely correlates with long-term survival. Neoplasia. 2006, 8: 879-884.PubMedCentralCrossRefPubMed
22.
Vlodavsky I, Ilan N, Naggi A, Casu B: Heparanase: structure, biological functions, and inhibition by heparin-derived mimetics of heparan sulfate. Curr Pharm Des. 2007, 13: 2057-2073.CrossRefPubMed
23.
Cohen-Kaplan V, Doweck I, Naroditsky I, Vlodavsky I, Ilan N: Heparanase augments epidermal growth factor receptor phosphorylation: correlation with head and neck tumor progression. Cancer Res. 2008, 68: 10077-10085.PubMedCentralCrossRefPubMed
24.
Nasser NJ: Heparanase involvement in physiology and disease. Cell Mol Life Sci. 2008, 65: 1706-1715.CrossRefPubMed
25.
Ilan N, Elkin M, Vlodavsky I: Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis. Int J Biochem Cell Biol. 2006, 38: 2018-2039.CrossRefPubMed
26.
Goldshmidt O, Zcharia E, Cohen M, Aingorn H, Cohen I, Nadav L, Katz BZ, Geiger B, Vlodavsky I: Heparanase mediates cell adhesion independent of its enzymatic activity. FASEB J. 2003, 17: 1015-1025.CrossRefPubMed
27.
Kuniyasu H, Chihara Y, Kubozoe T, Takahashi T: Co-expression of CD44v3 and heparanase is correlated with metastasis of human colon cancer. Int J Mol Med. 2002, 10: 333-337.PubMed
28.
Zetser A, Bashenko Y, Edovitsky E, Levy-Adam F, Vlodavsky I, Ilan N: Heparanase induces vascular endothelial growth factor expression: correlation with p38 phosphorylation levels and Src activation. Cancer Res. 2006, 66: 1455-1463.CrossRefPubMed
29.
Gingis-Velitski S, Zetser A, Kaplan V, Ben-Zaken O, Cohen E, Levy-Adam F, Bashenko Y, Flugelman MY, Vlodavsky I, Ilan N: Heparanase uptake is mediated by cell membrane heparan sulfate proteoglycans. J Biol Chem. 2004, 279: 44084-44092.CrossRefPubMed
30.
Gavard J, Patel V, Gutkind JS: Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering Src through mDia. Dev Cell. 2008, 14: 25-36.CrossRefPubMed
31.
Yang Y, Macleod V, Miao HQ, Theus A, Zhan F, Shaughnessy JD, Sawyer J, Li JP, Zcharia E, Vlodavsky I, Sanderson RD: Heparanase enhances syndecan-1 shedding: a novel mechanism for stimulation of tumor growth and metastasis. J Biol Chem. 2007, 282: 13326-13333.CrossRefPubMed
32.
Vaday GG, Lider O: Extracellular matrix moieties, cytokines, and enzymes: dynamic effects on immune cell behavior and inflammation. J Leukoc Biol. 2000, 67: 149-159.PubMed
33.
34.
Vlodavsky I, Miao HQ, Medalion B, Danagher P, Ron D: Involvement of heparan sulfate and related molecules in sequestration and growth promoting activity of fibroblast growth factor. Cancer Metastasis Rev. 1996, 15: 177-186.CrossRefPubMed
35.
Jiang LJ, Shao CK, He D, Li WG, Wu XZ, Cai DZ: Correlations of extrocellular matrix metalloproteinase inducer and microvessel density to invasiveness of ameloblastoma. Chinese J Cancer. 2008, 27: 1263-1266.
36.
Mikami S, Oya M, Shimoda M, Mizuno R, Ishida M, Kosaka T, Mukai M, Nakajima M, Okada Y: Expression of heparanase in renal cell carcinomas: implications for tumor invasion and prognosis. Clin Cancer Res. 2008, 14: 6055-6061.CrossRefPubMed
37.
Pantuck AJ, Zeng G, Belldegrun AS, Figlin RA: Pathobiology, prognosis, and targeted therapy for renal cell carcinoma: exploiting the hypoxia-induced pathway. Clin Cancer Res. 2003, 9: 4641-4652.PubMed
38.
Elmore JM, Kadesky KT, Koeneman KS, Sagalowsky AI: Reassessment of the 1997 TNM classification system for renal cell carcinoma. Cancer. 2003, 98: 2329-2334.CrossRefPubMed
39.
Sandlund J, Hedberg Y, Bergh A, Grankvist K, Ljungberg B, Rasmuson T: Evaluation of CD31 (PECAM-1) expression using tissue microarray in patients with renal cell carcinoma. Tumour Biol. 2007, 28: 158-164.CrossRefPubMed
40.
Fairweather JK, Hammond E, Johnstone KD, Ferro V: Synthesis and heparanase inhibitory activity of sulfated mannooligosaccharides related to the antiangiogenic agent PI-88. Bioorg Med Chem. 2008, 16: 699-709.CrossRefPubMed
41.
Lewis KD, Robinson WA, Millward MJ, Powell A, Price TJ, Thomson DB, Walpole ET, Haydon AM, Creese BR, Roberts KL, Zalcberg JR, Gonzalez R: A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma. Invest New Drugs. 2008, 26: 89-94.CrossRefPubMed
42.
Basche M, Gustafson DL, Holden SN, O'Bryant CL, Gore L, Witta S, Schultz MK, Morrow M, Levin A, Creese BR, Kangas M, Roberts K, Nguyen T, Davis K, Addison RS, Moore JC, Eckhardt SG: A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in patients with advanced solid tumors. Clin Cancer Res. 2006, 12: 5471-5480.CrossRefPubMed
Metadata
Title
Microvessel density and heparanase over-expression in clear cell renal cell cancer: correlations and prognostic significances
Authors
Juchao Ren
Hainan Liu
Lei Yan
Sujian Tian
Dawei Li
Zhonghua Xu
Publication date
01-12-2011
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2011
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-9-158

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