Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

Characterization of TEM1/endosialin in human and murine brain tumors

Eleanor B Carson-Walter1, Bethany N Winans1, Melissa C Whiteman1, Yang Liu1, Sally Jarvela2, Hannu Haapasalo2, Betty M Tyler3, David L Huso4, Mahlon D Johnson5 and Kevin A Walter16*

Author Affiliations

1 Department of Neurosurgery, The University of Rochester, Rochester, NY, USA

2 Department of Pathology, Tampere University Hospital, Tampere, Finland

3 Department of Neurosurgery, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

4 Department of Molecular and Comparative Pathobiology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

5 Department of Pathology, The University of Rochester, Rochester, NY, USA

6 James P Wilmot Cancer Center, The University of Rochester, Rochester, NY, USA

For all author emails, please log on.

BMC Cancer 2009, 9:417  doi:10.1186/1471-2407-9-417

Published: 30 November 2009

Abstract

Background

TEM1/endosialin is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern of TEM1/endosialin in astrocytic and metastatic brain tumors and investigated its role as a therapeutic target in human endothelial cells and mouse xenograft models.

Methods

In situ hybridization (ISH), immunohistochemistry (IH) and immunofluorescence (IF) were used to localize TEM1/endosialin expression in grade II-IV astrocytomas and metastatic brain tumors on tissue microarrays. Changes in TEM1/endosialin expression in response to pro-angiogenic conditions were assessed in human endothelial cells grown in vitro. Intracranial U87MG glioblastoma (GBM) xenografts were analyzed in nude TEM1/endosialin knockout (KO) and wildtype (WT) mice.

Results

TEM1/endosialin was upregulated in primary and metastatic human brain tumors, where it localized primarily to the tumor vasculature and a subset of tumor stromal cells. Analysis of 275 arrayed grade II-IV astrocytomas demonstrated TEM1/endosialin expression in 79% of tumors. Robust TEM1/endosialin expression occurred in 31% of glioblastomas (grade IV astroctyomas). TEM1/endosialin expression was inversely correlated with patient age. TEM1/endosialin showed limited co-localization with CD31, ╬▒SMA and fibronectin in clinical specimens. In vitro, TEM1/endosialin was upregulated in human endothelial cells cultured in matrigel. Vascular Tem1/endosialin was induced in intracranial U87MG GBM xenografts grown in mice. Tem1/endosialin KO vs WT mice demonstrated equivalent survival and tumor growth when implanted with intracranial GBM xenografts, although Tem1/endosialin KO tumors were significantly more vascular than the WT counterparts.

Conclusion

TEM1/endosialin was induced in the vasculature of high-grade brain tumors where its expression was inversely correlated with patient age. Although lack of TEM1/endosialin did not suppress growth of intracranial GBM xenografts, it did increase tumor vascularity. The cellular localization of TEM1/endosialin and its expression profile in primary and metastatic brain tumors support efforts to therapeutically target this protein, potentially via antibody mediated drug delivery strategies.