title: Endosialin and Associated Protein Expression in Soft Tissue Sarcomas: A Potential Target for Anti-Endosialin Therapeutic Strategies.
abstract: Endosialin (CD248, TEM-1) is expressed in pericytes, tumor vasculature, tumor fibroblasts, and some tumor cells, including sarcomas, with limited normal tissue expression, and appears to play a key role in tumor-stromal interactions, including angiogenesis. Monoclonal antibodies targeting endosialin have entered clinical trials, including soft tissue sarcomas. We evaluated a cohort of 94 soft tissue sarcoma samples to assess the correlation between gene expression and protein expression by immunohistochemistry for endosialin and PDGFR-β, a reported interacting protein, across available diagnoses. Correlations between the expression of endosialin and 13 other genes of interest were also examined. Within cohorts of soft tissue diagnoses assembled by tissue type (liposarcoma, leiomyosarcoma, undifferentiated sarcoma, and other), endosialin expression was significantly correlated with a better outcome. Endosialin expression was highest in liposarcomas and lowest in leiomyosarcomas. A robust correlation between protein and gene expression data for both endosialin and PDGFR-β was observed. Endosialin expression positively correlated with PDGFR-β and heparin sulphate proteoglycan 2 and negatively correlated with carbonic anhydrase IX. Endosialin likely interacts with a network of extracellular and hypoxia activated proteins in sarcomas and other tumor types. Since expression does vary across histologic groups, endosialin may represent a selective target in soft tissue sarcomas.
authors.affiliation: Translational Medicine and Diagnostics, Morphotek, Inc., Exton, PA 19341, USA.
authors.forename: Daniel J
authors.identifier: 0000-0002-2032-3742
authors.initials: DJ
authors.lastname: O'Shannessy
authors.affiliation: M2Gen, Tampa, FL 33612, USA; H. Lee Moffitt Cancer Center and Research Institute, Department of Biostatistics and Biostatistics, Tampa, FL 33612, USA.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Dai
authors.affiliation: M2Gen, Tampa, FL 33612, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Mitchell
authors.affiliation: M2Gen, Tampa, FL 33612, USA.
authors.forename: Shane
authors.initials: S
authors.lastname: Huntsman
authors.affiliation: M2Gen, Tampa, FL 33612, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Brantley
authors.affiliation: Department of Bioinformatics, Virginia Commonwealth University, Richmond, VA 23284, USA.
authors.forename: David
authors.initials: D
authors.lastname: Fenstermacher
authors.affiliation: Sarcoma Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Adolescent and Young Adult Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Damon R
authors.identifier: 0000-0002-8238-2465
authors.initials: DR
authors.lastname: Reed