Endothelial cell expression patterns
To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived from normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.
1. An isolated molecule comprising an antibody variable region which specifically binds to an extracellular domain of TEM 3 protein as shown in SEQ ID NO: 200.
2. The isolated molecule of claim 1 which is an in tact antibody molecule.
3. The isolated molecule of claim 1 which is a single chain variable region (ScFv).
4. The isolated molecule of claim 1 which is a monoclonal antibody.
5. The isolated molecule of claim 1 which is a humanized antibody.
6. The isolated molecule of claim 1 which is a human antibody.
7. The isolated molecule of claim 1 which is bound to a cytotoxic moiety.
8. The isolated molecule of claim 1 which is bound to a therapeutic moiety.
9. The isolated molecule of claim 1 which is bound to a detectable moiety.
10. The isolated molecule of claim 1 which is bound to an anti-tumor agent.
11. A method of inhibiting neoangiogenesis, comprising:
administering to a subject in need thereof an effective amount of an isolated molecule comprising an antibody variable region which specifically binds to an extracellular domain of TEM 3 protein as shown in SEQ ID NO: 200, whereby neoangiogenesis is inhibited.
12. The method of claim 11 wherein the subject bears a vascularized tumor.
13. The method of claim 11 wherein the subject has polycystic kidney disease.
14. The method of claim 11 wherein the subject has diabetic retinopathy.
15. The method of claim 11 wherein the subject has rheumatoid arthritis.
16. The method of claim 11 wherein the subject has psoriasis.
17. A method of inhibiting tumor growth, comprising:
administering to a human subject bearing a tumor an effective amount of an isolated molecule comprising an antibody variable region which specifically binds to an extracellular domain of TEM 3 protein as shown in SEQ ID NO: 200, whereby growth of the tumor is inhibited.
18. An isolated molecule comprising an antibody variable region which specifically binds to TEM 3 protein as shown in SEQ ID NO: 200.
19. The isolated molecule of claim 18 which is a single chain variable region (ScFv).
20. The isolated molecule of claim 18 which is a monoclonal antibody.
21. The isolated molecule of claim 18 which is a humanized antibody.
22. The isolated molecule of claim 18 which is a human antibody.
23. The isolated molecule of claim 18 which is bound to a cytotoxic moiety.
24. The isolated molecule of claim 18 which is bound to a therapeutic moiety.
25. The isolated molecule of claim 18 which is bound to a detectable moiety.
26. The isolated molecule of claim 18 which is bound to an anti-tumor agent.
27. The isolated molecule of claim 18 which is an in tact antibody molecule.