Tumor endothelial marker 7 (TEM-7): A novel target for antiangiogenic therapy

被引:22
|
作者
Bagley, Rebecca G. [1 ]
Rouleau, Cecile [1 ]
Weber, William [1 ]
Mehraein, Khodadad [2 ]
Smale, Robert [2 ]
Curiel, Maritza [2 ]
Callahan, Michelle [1 ]
Roy, Andre [1 ]
Boutin, Paula [1 ]
St Martin, Thia [1 ]
Nacht, Mariana [1 ]
Teicher, Beverly A. [1 ]
机构
[1] Genzyme Corp, Framingham, MA 01701 USA
[2] Genzyme Genet, Los Angeles, CA 90066 USA
关键词
EXTRACELLULAR-MATRIX; PRECURSOR CELLS; EXPRESSION; CANCER; IDENTIFICATION; ANGIOGENESIS; CONTRIBUTE; CORTACTIN; PROTEINS; GROWTH;
D O I
10.1016/j.mvr.2011.09.004
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Antiangiogenesis has been validated as a therapeutic strategy to treat cancer, however, a need remains to identify new targets and therapies for specific diseases and to improve clinical benefit from antiangiogenic agents. Tumor endothelial marker 7 (TEM-7) was investigated as a possible target for therapeutic antiangiogenic intervention in cancer. TEM-7 expression was assessed by in situ hybridization or by immunohistochemistry (IHC) in 130 formalin-fixed paraffin-embedded (FFPE) and 410 frozen human clinical specimens of cancer plus 301 normal tissue samples. In vitro TEM-7 expression was evaluated in 4 human endothelial cell models and in 32 human cancer cell lines by RT-PCR and flow cytometry. An anti-TEM-7 antibody was tested in vitro on human SKOV3 ovarian and MDA-MB-231 breast carcinoma cells that expressed TEM-7 in antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis assays. In frozen tumor tissues, TEM-7 mRNA and protein was detected in all but one of the cancer types tested and was infrequently expressed in normal frozen tissues. In FFPE tumor tissues. TEM-7 protein was detected by IHC in colon, breast, lung, bladder, ovarian and endometrial cancers and in sarcomas. TEM-7 protein was not detected in head and neck, prostate or liver cancers. TEM-7 expression was restricted to the vasculature and was absent from tumor cells. In vitro, TEM-7 was not detected in human microvascular endothelial cells (HMVEC) or human umbilical vein endothelial cells (HUVEC) but was induced in endothelial precursor/progenitor cells (EPC) in the presence of the mitogen phorbol ester PMA. An anti-TEM-7 antibody mediated ADCC and phagocytosis in SKOV3 and MDA-MB-231 cell lines infected with an adenovirus expressing TEM-7. These data demonstrate that TEM-7 is a vascular protein associated with angiogenic states. TEM-7 is a novel and attractive target for antiangiogenic therapy. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:253 / 262
页数:10
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