title: Functional assessment of von Willebrand factor expression by cancer cells of non-endothelial origin.
abstract: Von Willebrand factor (VWF) is a highly adhesive procoagulant molecule that mediates platelet adhesion to endothelial and subendothelial surfaces. Normally it is expressed exclusively in endothelial cells (ECs) and megakaryocytes. However, a few studies have reported VWF detection in cancer cells of non-endothelial origin, including osteosarcoma. A role for VWF in cancer metastasis has long been postulated but evidence supporting both pro- and anti-metastatic roles for VWF has been presented. We hypothesized that the role of VWF in cancer metastasis is influenced by its cellular origin and that cancer cell acquisition of VWF expression may contribute to enhanced metastatic potential. We demonstrated de novo expression of VWF in glioma as well as osteosarcoma cells. Endothelial monolayer adhesion, transmigration and extravasation capacities of VWF expressing cancer cells were shown to be enhanced compared to non-VWF expressing cells, and were significantly reduced as a result of VWF knock down. VWF expressing cancer cells were also detected in patient tumor samples of varying histologies. Analyses of the mechanism of transcriptional activation of the VWF in cancer cells demonstrated a pattern of trans-activating factor binding and epigenetic modifications consistent overall with that observed in ECs. These results demonstrate that cancer cells of non-endothelial origin can acquire de novo expression of VWF, which can enhance processes, including endothelial and platelet adhesion and extravasation, that contribute to cancer metastasis.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Anahita
authors.initials: A
authors.lastname: Mojiri
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Stoletov
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Maria Areli Lorenzana
authors.initials: MA
authors.lastname: Carrillo
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Lian
authors.initials: L
authors.lastname: Willetts
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Saket
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Roseline
authors.initials: R
authors.lastname: Godbout
authors.affiliation: Department of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Jurasz
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Consolato M
authors.initials: CM
authors.lastname: Sergi
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.|Departments of Medical Genetics and Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: David D
authors.initials: DD
authors.lastname: Eisenstat
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Lewis
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Nadia
authors.initials: N
authors.lastname: Jahroudi
mesh_terms: D000818:Animals; D002642:Chick Embryo; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D012516:Osteosarcoma / Q000473:pathology*; D014841:von Willebrand Factor / Q000096:biosynthesis*
chemical_list: D014841:von Willebrand Factor
keywords: cancer; extravasation; transcription; transcription factor; von Willebrand factor