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Identification of a Binding Partner for the Endothelial Cell Surface Proteins TEM7 and TEM7R

¹ The Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center and Program in Human Genetics and Molecular Biology, Johns Hopkins Medical Institutions, Baltimore, Maryland; ² Department of Pathology, University of South Carolina School of Medicine, South Carolina Cancer Center, Division of Basic Research, Columbia, South Carolina; ³ Genzyme Molecular Oncology, Framingham, Massachusetts; ⁴ Imgenex Corporation, San Diego, California; and ⁵ Tumor Angiogenesis Section, Mouse Cancer Genetics Program, National Cancer Institute at Frederick, Frederick, Maryland

Tumor endothelial marker 7 (TEM7) was recently identified as an mRNA transcript overexpressed in the blood vessels of human solid tumors. Here, we identify several new variants of TEM7, derived by alternative splicing, that are predicted to be intracellular (TEM7-I), secreted (TEM7-S), or on the cell surface membrane (TEM7-M) of tumor endothelium. Using new antibodies against the TEM7 protein, we confirmed the predicted expression of TEM7 on the cell surface and demonstrated that TEM7-M protein, like its mRNA, is overexpressed on the endothelium of various tumor types. We then used an affinity purification strategy to search for TEM7-binding proteins and identified cortactin as a protein capable of binding to the extracellular region of both TEM7 and its closest homologue, TEM7-related (TEM7R), which is also expressed in tumor endothelium. The binding domain of cortactin was mapped to a unique nine-amino acid region in its plexin-like domain. These studies establish the overexpression of TEM7 protein in tumor endothelium and provide new opportunities for the delivery of therapeutic and imaging agents to the vessels of solid tumors.

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