Identification of a binding partner for the endothelial cell surface proteins TEM7 and TEM7R.
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.
Nanda
Akash
A
The Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Buckhaults
Phillip
P
Seaman
Steven
S
Agrawal
Nishant
N
Boutin
Paula
P
Shankara
Srinivas
S
Nacht
Mariana
M
Teicher
Beverly
B
Stampfl
Jason
J
Singh
Sujay
S
Vogelstein
Bert
B
Kinzler
Kenneth W
KW
St Croix
Brad
B
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002846:Chromatography, Affinity; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger