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Characterization of tumor endothelia...

Nanda, Akash.

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Characterization of tumor endothelial markers.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Characterization of tumor endothelial markers./
Author:	Nanda, Akash.
Description:	95 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-04, Section: B, page: 1901.
Contained By:	Dissertation Abstracts International66-04B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3172661
ISBN:	0542103354

Characterization of tumor endothelial markers.
Nanda, Akash.

Characterization of tumor endothelial markers. - 95 p.

Source: Dissertation Abstracts International, Volume: 66-04, Section: B, page: 1901.

Thesis (Ph.D.)--The Johns Hopkins University, 2005.

Tumor Endothelial Markers (TEMs) represent novel molecular targets for cancer therapy. They were recently identified using SAGE which compared global gene expression patterns of endothelial cells derived from blood vessels of normal and malignant colorectal tissues. From both a biological and clinical standpoint, those TEMs associated with the cell-surface membrane are of particular interest. Accordingly, we have attempted to further characterize five such genes, TEMs 1, 5, 7, 7R, and 8, all of which encode putative cell-surface receptors. We began by identifying mouse counterparts to each of these genes and examining their expression patterns in mouse tumors, embryos, and adult tissues. Our results demonstrate that these TEMs are abundantly expressed in tumor vessels and the vasculature of the developing embryo, but virtually undetectable in normal adult mouse tissues. We have also developed a new panel of monoclonal antibodies to assess the protein expression patterns of TEM7 and TEM8 in human tissues. We demonstrate that TEM7 and TEM8 protein is preferentially expressed in the endothelial cells of a variety of neoplastic tissue. We also used the extracellular domain of TEM8 as bait in a yeast two-hybrid screen to search for ligands and identified the alpha 3 subunit of collagen VI as an interacting partner. The TEM8-interacting region on collagen alpha 3(VI) was mapped to its COOH-terminal C5 domain. Using RT-PCR we have identified new variants of TEM7, derived by alternative splicing, that are predicted to be intracellular (TEM7-I) and secreted (TEM7-S). We have 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 TEM7R. The binding domain of cortactin was mapped to a unique nine-amino acid region in its plexin-like domain. The results of our collective findings demonstrate conservation of human and mouse tumor angiogenesis at the molecular level and provide further evidence that TEMs represent novel and specific cancer targets at the protein level. Furthermore, the development of monoclonal antibodies and identification of ligands provide novel reagents which can now be tested as therapeutic and imaging agents in preclinical animal models.

ISBN: 0542103354Subjects--Topical Terms:

1017719
Biology, Molecular.

Characterization of tumor endothelial markers.
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500 $a Source: Dissertation Abstracts International, Volume: 66-04, Section: B, page: 1901.
500 $a Advisers: Bert Vogelstein; Kenneth W. Kinzler.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2005.
520 $a Tumor Endothelial Markers (TEMs) represent novel molecular targets for cancer therapy. They were recently identified using SAGE which compared global gene expression patterns of endothelial cells derived from blood vessels of normal and malignant colorectal tissues. From both a biological and clinical standpoint, those TEMs associated with the cell-surface membrane are of particular interest. Accordingly, we have attempted to further characterize five such genes, TEMs 1, 5, 7, 7R, and 8, all of which encode putative cell-surface receptors. We began by identifying mouse counterparts to each of these genes and examining their expression patterns in mouse tumors, embryos, and adult tissues. Our results demonstrate that these TEMs are abundantly expressed in tumor vessels and the vasculature of the developing embryo, but virtually undetectable in normal adult mouse tissues. We have also developed a new panel of monoclonal antibodies to assess the protein expression patterns of TEM7 and TEM8 in human tissues. We demonstrate that TEM7 and TEM8 protein is preferentially expressed in the endothelial cells of a variety of neoplastic tissue. We also used the extracellular domain of TEM8 as bait in a yeast two-hybrid screen to search for ligands and identified the alpha 3 subunit of collagen VI as an interacting partner. The TEM8-interacting region on collagen alpha 3(VI) was mapped to its COOH-terminal C5 domain. Using RT-PCR we have identified new variants of TEM7, derived by alternative splicing, that are predicted to be intracellular (TEM7-I) and secreted (TEM7-S). We have 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 TEM7R. The binding domain of cortactin was mapped to a unique nine-amino acid region in its plexin-like domain. The results of our collective findings demonstrate conservation of human and mouse tumor angiogenesis at the molecular level and provide further evidence that TEMs represent novel and specific cancer targets at the protein level. Furthermore, the development of monoclonal antibodies and identification of ligands provide novel reagents which can now be tested as therapeutic and imaging agents in preclinical animal models.
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