title: HABP2 is a Novel Regulator of Hyaluronan-Mediated Human Lung Cancer Progression.
abstract: BACKGROUND
  Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA), which we have previously demonstrated can regulate the activity of the extracellular serine protease, hyaluronan binding protein 2 (HABP2). This study examined the functional role of HABP2 on HA-mediated human lung cancer dynamics.
  
  
  METHODS
  Immunohistochemical analysis was performed on lung cancer patient samples using anti-HABP2 antibody. Stable control, shRNA, and HABP2 overexpressing human lung adenocarcinoma cells were evaluated using immunoblot analysis, migration, extravasation, and urokinase plasminogen activator (uPA) activation assays with or without high-molecular weight HA or low-molecular weight HA (LMW-HA). In human lung cancer xenograft models, primary tumor growth rates and lung metastasis were analyzed using consecutive tumor volume measurements and nestin immunoreactivity in nude mouse lungs.
  
  
  RESULTS
  We provide evidence that HABP2 is an important regulator of lung cancer progression. HABP2 expression was increased in several subtypes of patient non-small cell lung cancer samples. Further, HABP2 overexpression increased LMW-HA-induced uPA activation, migration, and extravasation in human lung adenocarcinoma cells. In vivo, overexpression of HABP2 in human lung adenocarcinoma cells increased primary tumor growth rates in nude mice by ~2-fold and lung metastasis by ~10-fold compared to vector control cells (n = 5/condition).
  
  
  CONCLUSIONS
  Our data suggest a possible direct effect of HABP2 on uPA activation and lung cancer progression. Our observations suggest that exploration of HABP2 in non-small cell lung carcinoma merits further study both as a diagnostic and therapeutic option.
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, Pritzker School of Medicine, The University of Chicago , Chicago, IL , USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Mirzapoiazova
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, Pritzker School of Medicine, The University of Chicago , Chicago, IL , USA.
authors.forename: Nurbek
authors.initials: N
authors.lastname: Mambetsariev
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, Pritzker School of Medicine, The University of Chicago , Chicago, IL , USA ; Section of Hematology/Oncology, Department of Medicine, Pritzker School of Medicine, The University of Chicago , Chicago, IL , USA.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lennon
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, Pritzker School of Medicine, The University of Chicago , Chicago, IL , USA.
authors.forename: Bolot
authors.initials: B
authors.lastname: Mambetsariev
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, Pritzker School of Medicine, The University of Chicago , Chicago, IL , USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Berlind
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, Pritzker School of Medicine, The University of Chicago , Chicago, IL , USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, Pritzker School of Medicine, The University of Chicago , Chicago, IL , USA ; Department of Anesthesia and Critical Care, Pritzker School of Medicine, The University of Chicago , Chicago, IL , USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Singleton
keywords: HABP2; hyaluronan; non-small cell lung cancer; transendothelial extravasation; urokinase plasminogen activator