title: Heparanase expression and localization in different types of human lung cancer.
abstract: BACKGROUND
  Heparanase is the only known mammalian glycosidase capable of cleaving heparan sulfate chains. The expression of this enzyme has been associated with tumor development because of its ability to degrade extracellular matrix and promote cell invasion.
  
  
  METHODS
  We analyzed heparanase expression in lung cancer samples to understand lung tumor progression and malignancy. Of the samples from 37 patients, there were 14 adenocarcinomas, 13 squamous cell carcinomas, 5 large cell carcinomas, and 5 small cell carcinomas. Immunohistochemistry was performed to ascertain the expression and localization of heparanase.
  
  
  RESULTS
  All of the tumor types expressed heparanase, which was predominantly localized within the cytoplasm and nucleus. Significant enzyme expression was also observed in cells within the tumor microenvironment, such as fibroblasts, epithelial cells, and inflammatory cells. Adenocarcinomas exhibited the strongest heparanase staining intensity and the most widespread heparanase distribution. Squamous cell carcinomas, large cell carcinomas, and small cell carcinomas had a similar subcellular distribution of heparanase to adenocarcinomas but the distribution was less widespread. Heparanase expression tended to correlate with tumor node metastasis (TNM) staging in non-small cell lung carcinoma.
  
  
  CONCLUSIONS
  In this study, we showed that heparanase was localized to the cytoplasm and nucleus of tumor cells and to cells within the microenvironment in different types of lung cancer. This enzyme exhibited a differential distribution based on the type of lung tumor. General significance Elucidating the heparanase expression patterns in different types of lung cancer increased our understanding of the crucial role of heparanase in lung cancer biology. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
authors.affiliation: Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Teresa Cristina
authors.initials: TC
authors.lastname: Fernandes dos Santos
authors.affiliation: Laboratório de Bioquímica e Biologia Celular de Glicoconjugados, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Angélica Maciel
authors.initials: AM
authors.lastname: Gomes
authors.affiliation: Instituto de Doenças do Tórax, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcos Eduardo Machado
authors.initials: ME
authors.lastname: Paschoal
authors.affiliation: Laboratório de Bioquímica e Biologia Celular de Glicoconjugados, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mariana Paranhos
authors.initials: MP
authors.lastname: Stelling
authors.affiliation: Laboratório de Imunologia Tumoral, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vivian Mary Barral Dodd
authors.initials: VM
authors.lastname: Rumjanek
authors.affiliation: Laboratório Multidisciplinar de Pesquisa, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Alyson do Rosário
authors.initials: Ado R
authors.lastname: Junior
authors.affiliation: Serviço de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Paulo Marcos
authors.initials: PM
authors.lastname: Valiante
authors.affiliation: Serviço de Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Kalil
authors.initials: K
authors.lastname: Madi
authors.affiliation: Laboratório Multidisciplinar de Pesquisa, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Heitor Siffert
authors.initials: HS
authors.lastname: Pereira de Souza
authors.affiliation: Laboratório de Bioquímica e Biologia Celular de Glicoconjugados, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: mpavao@hucff.ufrj.br.
authors.forename: Mauro Sergio Gonçalves
authors.initials: MS
authors.lastname: Pavão
authors.affiliation: Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: morganalima@ufrj.br.
authors.forename: Morgana Teixeira Lima
authors.initials: MT
authors.lastname: Castelo-Branco
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D002454:Cell Differentiation; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology / Q000473:pathology; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification* / Q000201:enzymology* / Q000473:pathology; D008214:Lymphocytes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D021381:Protein Transport; D013194:Staining and Labeling; D059016:Tumor Microenvironment; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase
keywords: Adenocarcinoma; Heparanase; Large cell carcinoma; Small cell carcinoma; Squamous cell carcinoma