Analysis of heparanase isoforms and cathepsin B in the plasma of patients with gastrointestinal carcinomas

analytical cross-sectional study

Authors

  • Carina Mucciolo Melo Universidade Federal de São Paulo (Unifesp)
  • Clarice Silvia Taemi Origassa Universidade Federal de São Paulo (Unifesp)
  • Thérèse Rachell Theodoro Faculdade de Medicina do ABC (FMABC)
  • Leandro Luongo Matos Faculdade de Medicina do ABC (FMABC)
  • Thaís Aguilar Miranda Universidade Federal de São Paulo (Unifesp)
  • Camila Melo Accardo Universidade Federal de São Paulo (Unifesp)
  • Rodrigo Ippolito Bouças Universidade Federal de São Paulo (Unifesp)
  • Eloah Rabello Suarez Universidade Federal de São Paulo (Unifesp)
  • Madalena Maria Nunes Silva Pares Associação Beneficente de Coleta de Sangue (Colsan)
  • Daniel Reis Waisberg Universidade de São Paulo (USP)
  • Giovanna Canato Toloi Faculdade de Medicina do ABC (FMABC)
  • Helena Bonciani Nader Universidade Federal de São Paulo (Unifesp)
  • Jaques Waisberg Faculdade de Medicina do ABC (FMABC)
  • Maria Aparecida Silva Pinhal Faculdade de Medicina do ABC (FMABC)

Keywords:

Glucuronidase, Cathepsin B, Tumor markers, biological, Carcinoma, Plasma

Abstract

CONTEXT AND OBJECTIVE: Heparanase-1 degrades heparan sulfate and has been correlated with tumor progression. Although the isoform heparanase-2 has no catalytic activity, it seems to be important for modulating heparanase-1 activity. Cathepsin B is a proteinase involved in tumor metastasis. The aim of this study was to analyze heparanase isoform expression and cathepsin B activity in plasma samples from patients with gastrointestinal carcinomas, compared with healthy individuals (control group). DESIGN AND SETTING: This was an analytical cross-sectional study. Peripheral blood samples were col-lected at a Brazilian public hospital, from 21 patients with histopathological diagnoses of gastrointestinal carcinomas and from 43 healthy individuals. The analyses were performed in two Brazilian medical schools. METHODS: Heparanase isoforms were identified and quantified in plasma samples by means of Western blot. The enzymatic activities of heparanase-1 and cathepsin B were also measured. RESULTS: The results demonstrated that the expression of both heparanase isoforms was significantly greater in plasma samples from gastrointestinal carcinoma patients, compared with the control group. Logistic regression analysis showed that increased heparanase-1 and heparanase-2 expression was exclu-sively dependent on the tumor. There was a significant increase in heparanase-1 and cathepsin B activity in the patients’ plasma. CONCLUSION: Overexpression of heparanase-1 and heparanase-2, along with increased heparanase-1 and cathepsin B activity in plasma, is associated with the diagnosis of gastrointestinal carcinoma. These findings provide support for using non-invasive assays (plasma samples) as an auxiliary method for diag-nosing gastrointestinal tumors.

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Author Biographies

Carina Mucciolo Melo, Universidade Federal de São Paulo (Unifesp)

MSc. Doctoral Student, Department of Biochemistry, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.

Clarice Silvia Taemi Origassa, Universidade Federal de São Paulo (Unifesp)

MSc. Doctoral Student, Department of Biochemistry, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.

Thérèse Rachell Theodoro, Faculdade de Medicina do ABC (FMABC)

MSc. Doctoral Student, Faculdade de Medicina do ABC (FMABC), Santo André, São Paulo, Brazil.

Leandro Luongo Matos, Faculdade de Medicina do ABC (FMABC)

MD, PhD. Associate Professor, Department of Biochemistry, Faculdade de Medicina do ABC (FMABC), Santo André, São Paulo, Brazil.

Thaís Aguilar Miranda, Universidade Federal de São Paulo (Unifesp)

MSc. Research Collaborator, Department of Biochemistry, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.

Camila Melo Accardo, Universidade Federal de São Paulo (Unifesp)

PhD. Postdoctoral Student, Department of Biochemistry, Universidade Federal de São Paulo (Unifesp),  São Paulo, Brazil.

Rodrigo Ippolito Bouças, Universidade Federal de São Paulo (Unifesp)

PhD. Research Collaborator, Department of Biochemistry, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.

Eloah Rabello Suarez, Universidade Federal de São Paulo (Unifesp)

PhD. Postdoctoral Student, Department of Biochemistry, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.

Madalena Maria Nunes Silva Pares, Associação Beneficente de Coleta de Sangue (Colsan)

PhD. Research Collaborator, Associação Beneficente de Coleta de Sangue (Colsan), São Paulo, São Paulo, Brazil.

Daniel Reis Waisberg, Universidade de São Paulo (USP)

MD. Attending Physician. Surgery Department, Universidade de São Paulo (USP), São Paulo, Brazil.

Giovanna Canato Toloi, Faculdade de Medicina do ABC (FMABC)

Medical Student. Faculdade de Medicina do ABC (FMABC), Santo André, São Paulo, Brazil.

Helena Bonciani Nader, Universidade Federal de São Paulo (Unifesp)

PhD. Titular Professor, Department of Biochemistry, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.

Jaques Waisberg, Faculdade de Medicina do ABC (FMABC)

MD, PhD. Adjunct Professor, Department of Surgery, Faculdade de Medicina do ABC (FMABC), Santo André, São Paulo, Brazil.

Maria Aparecida Silva Pinhal, Faculdade de Medicina do ABC (FMABC)

PhD. Titular Professor, Department of Biochemistry, Faculdade de Medicina do ABC (FMABC), Santo André, São Paulo, Brazil.

References

Cancer Research UK. World cancer factsheet A3. Available from: http://publications.cancerresearchuk.org/downloads/Product/CS_FS_WORLD_A3.pdf. Accessed in 2013 (Nov 13).

Brasil. Ministério da Saúde. Instituto Nacional de Câncer. Câncer de fígado. Available from: http://www.inca.gov.br/conteudo_view.asp?id=330. Accessed in 2013 (Nov 13).

Arregi MMU, Férrer DPC, Assis ECV, et al. Perfil clínico-epidemiológico das neoplasias de estômago atendidas no Hospital do Câncer do Instituto do Câncer do Ceará, no período 2000-2004 [Clinical-epidemiological profile of gastric neoplasms in the cancer Hostpital of Ceara’s Cancer Institute, from the period 2000-2004]. Rev Bras Cancerol. 2009;55(2):121-8.

Wakatsuki T, Irisawa A, Takagi T, et al. Primary adenocarcinoma of the minor duodenal papilla. Yonsei Med J. 2008;49(2):333-6.

Devuni D, Birk JW. Papillary tumors. Medscape. Available from: http://emedicine.medscape.com/article/187464-overview#a1/. Accessed in 2014 (Jan 27).

National Cancer Institute. What You Need To Know About™ Cancer of the Colon and Rectum. Available from: http://www.cancer.gov/cancertopics/wyntk/colon-and-rectal/. Accessed in 2014 (Jan 27).

Queiroga RC, Pernambuco, AP. Câncer de esôfago: epidemiologia, diagnóstico e tratamento [Esophageal cancer: epidemiology, diagnosis and treatment]. Rev Bras Cancerol. 2005;52(2):173-8.

Chen JQ, Zhan WH, He YL, et al. Expression of heparanase gene, CD44v6, MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas. World J Gastroenterol. 2004;10(6):776-82.

Vlodavsky I, Friedmann Y, Elkin M, et al. Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nat Med. 1999;5(7):793-802.

Hulett MD, Freeman C, Hamdorf BJ, et al. Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nat Med. 1999;5(7):803-9.

Naomoto Y, Takaoka M, Okawa T, et al. The role of heparanase in gastrointestinal cancer (Review). Oncol Rep. 2005;14(1):3-8.

Vlodavsky I, Eldor A, Haimovitz-Friedman A, et al. Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation. Invasion Metastasis. 1992;12(2):112-27.

Vlodavsky I, Goldshmidt O, Zcharia E, et al. Molecular properties and involvement of heparanase in cancer progression and normal development. Biochimie. 2001;83(8):831-9.

McKenzie E, Tyson K, Stamps A, et al. Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member. Biochem Biophys Res Commun. 2000;276(3):1170-7.

Baker E, Crawford J, Sutherland GR, et al. Human HPA endoglycosidase heparanase. Map position 4q21.3. Chromosome Res. 1999;7(4):319.

Vlodavsky I, Goldshmidt O. Properties and function of heparanase in cancer metastasis and angiogenesis. Haemostasis. 2001;31 Suppl 1:60-3.

Dempsey LA, Brunn GJ, Platt JL. Heparanase, a potential regulator of cell-matrix interactions. Trends Biochem Sci. 2000;25(8):349-51.

Marchetti D, Li J, Shen R. Astrocytes contribute to the brain-metastatic specificity of melanoma cells by producing heparanase. Cancer Res. 2000;60(17):4767-70.

Goldshmidt O, Zcharia E, Cohen M, et al. Heparanase mediates cell adhesion independent of its enzymatic activity. FASEB J. 2003;17(9):1015-25.

Nadav L, Eldor A, Yacoby-Zeevi O, et al. Activation, processing and trafficking of extracellular heparanase by primary human fibroblasts. J Cell Sci. 2002;115(Pt 10):2179-87.

Levy-Adam F, Feld S, Cohen-Kaplan V, et al. Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity. J Biol Chem. 2010;285(36):28010-9.

Yan S, Sameni M, Sloane BF. Cathepsin B and human tumor progression. Biol Chem. 1998;379(2):113-23.

Eldor A, Bar-Ner M, Yahalom J, Fuks Z, Vlodavsky I. Role of heparanase in platelet and tumor cell interactions with the subendothelial extracellular matrix. Semin Thromb Hemost. 1987;13(4):475-88.

Ishai-Michaeli R, Eldor A, Vlodavsky I. Heparanase activity expressed by platelets, neutrophils, and lymphoma cells releases active fibroblast growth factor from extracellular matrix. Cell Regul. 1990;1(11):833-42.

Bouças RI, Trindade ES, Tersariol IL, Dietrich CP, Nader HB. Development of an enzyme-linked immunosorbent assay (ELISA)-like fluorescence assay to investigate the interactions of glycosaminoglycans to cells. Anal Chim Acta. 2008;618(2):218-26.

Almeida PC, Nantes IL, Chagas JR, et al. Cathepsin B activity regulation. Heparin-like glycosaminoglycans protect human cathepsin B from alkaline pH-induced inactivation. J Biol Chem. 2001;276(2):944-51.

Friedmann Y, Vlodavsky I, Aingorn H, et al. 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(4):1167-75.

Dreyfuss JL, Regatieri CV, Jarrouge TR, et al. Heparan sulfate proteoglycans: structure, protein interactions and cell signaling. An Acad Bras Cienc. 2009;81(3):409-29.

Sanderson RD, Yang Y, Kelly T, et al. Enzymatic remodeling of heparan sulfate proteoglycans within the tumor microenvironment: growth regulation and the prospect of new cancer therapies. J Cell Biochem. 2005;96(5):897-905.

Vreys V, David G. Mammalian heparanase: what is the message? J Cell Mol Med. 2007;11(3):427-52.

Theodoro TR, de Matos LL, SantAnna AV, et al. Heparanase expression in circulating lymphocytes of breast cancer patients depends on the presence of the primary tumor and/or systemic metastasis. Neoplasia. 2007;9(6):504-10.

Takaoka M, Naomoto Y, Ohkawa T, et al. Heparanase expression correlates with invasion and poor prognosis in gastric cancers. Lab Invest. 2003;83(5):613-22.

Giordano RJ. Heparanase-2 and syndecan-1 in colon cancer: the ugly ducklings or the beautiful swans? Eur J Gastroenterol Hepatol. 2008;20(8):716-8.

Peretti T, Waisberg J, Mader AM, et al. Heparanase-2, syndecan-1, and extracellular matrix remodeling in colorectal carcinoma. Eur J Gastroenterol Hepatol. 2008;20(8):756-65.

Marques RM, Focchi GR, Theodoro TR, et al. The immunoexpression of heparanase 2 in normal epithelium, intraepithelial, and invasive squamous neoplasia of the cervix. J Low Genit Tract Dis. 2012;16(3):256-62.

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Published

2015-01-01

How to Cite

1.
Melo CM, Origassa CST, Theodoro TR, Matos LL, Miranda TA, Accardo CM, Bouças RI, Suarez ER, Pares MMNS, Waisberg DR, Toloi GC, Nader HB, Waisberg J, Pinhal MAS. Analysis of heparanase isoforms and cathepsin B in the plasma of patients with gastrointestinal carcinomas: analytical cross-sectional study. Sao Paulo Med J [Internet]. 2015 Jan. 1 [cited 2025 Mar. 9];133(1):28-35. Available from: https://periodicosapm.emnuvens.com.br/spmj/article/view/1004

Issue

Vol. 133 No. 1 (2015)

Section

Original Article

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