scholarly journals Active Immunization Against the Vascular Endothelial Growth Factor Receptor flk1 Inhibits Tumor Angiogenesis and Metastasis

2002 ◽  
Vol 195 (12) ◽  
pp. 1575-1584 ◽  
Author(s):  
Yiwen Li ◽  
Mei-Nai Wang ◽  
Hongli Li ◽  
Karen D. King ◽  
Rajiv Bassi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Angiogenesis ◽  
Active Immunization ◽  
Active Immunotherapy ◽  
Cytotoxic T Cell ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Lewis Lung ◽  
Endothelial Growth Factor

The vascular endothelial growth factor (VEGF) receptor fetal liver kinase 1 (flk1; VEGFR-2, KDR) is an endothelial cell–specific receptor tyrosine kinase that mediates physiological and pathological angiogenesis. We hypothesized that an active immunotherapy approach targeting flk1 may inhibit tumor angiogenesis and metastasis. To test this hypothesis, we first evaluated whether immune responses to flk1 could be elicited in mice by immunization with dendritic cells pulsed with a soluble flk1 protein (DC-flk1). This immunization generated flk1-specific neutralizing antibody and CD8+ cytotoxic T cell responses, breaking tolerance to self-flk1 antigen. Tumor-induced angiogenesis was suppressed in immunized mice as measured in an alginate bead assay. Development of pulmonary metastases was strongly inhibited in DC-flk1–immunized mice challenged with B16 melanoma or Lewis lung carcinoma cells. DC-flk1 immunization also significantly prolonged the survival of mice challenged with Lewis lung tumors. Thus, an active immunization strategy that targets an angiogenesis-related antigen on endothelium can inhibit angiogenesis and may be a useful approach for treating angiogenesis-related diseases.

Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 546-553 ◽  
Author(s):  
Hajime Kubo ◽  
Takashi Fujiwara ◽  
Lotta Jussila ◽  
Hiroyuki Hashi ◽  
Minetaro Ogawa ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Angiogenesis ◽  
Vascular Endothelial Cells ◽  
Lymphatic Vessels ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Endothelial Lining ◽  
Tumor Bearing ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) plays a major role in tumor angiogenesis. VEGF-C, however, is thought to stimulate the growth of lymphatic vessels because an expression of its specific receptor, VEGF receptor-3 (VEGFR-3), was demonstrated to be restricted to lymphatic vessels. Here we demonstrate that the inactivation of VEGFR-3 by a novel blocking monoclonal antibody (mAb) suppresses tumor growth by inhibiting the neo-angiogenesis of tumor-bearing tissues. Although VEGFR-3 is not expressed in adult blood vessels, it is induced in vascular endothelial cells of the tumor-bearing tissues. Hence, VEGFR-3 is another receptor tyrosine kinase involved in tumor-induced angiogenesis. Micro-hemorrhage in the tumor-bearing tissue was the most conspicuous histologic finding specific to AFL4 mAb-treated mice. Scanning microscopy demonstrated disruptions of the endothelial lining of the postcapillary venule, probably the cause of micro-hemorrhage and the subsequent collapse of the proximal vessels. These findings suggest the involvement of VEGFR-3 in maintaining the integrity of the endothelial lining during angiogenesis. Moreover, our results suggest that the VEGF-C/VEGFR-3 pathway may serve another candidate target for cancer therapy.

Involvement of vascular endothelial growth factor receptor-3 in maintenance of integrity of endothelial cell lining during tumor angiogenesis

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 546-553 ◽  
Author(s):  
Hajime Kubo ◽  
Takashi Fujiwara ◽  
Lotta Jussila ◽  
Hiroyuki Hashi ◽  
Minetaro Ogawa ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Angiogenesis ◽  
Vascular Endothelial Cells ◽  
Lymphatic Vessels ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Endothelial Lining ◽  
Tumor Bearing ◽  
Endothelial Growth Factor

Abstract Vascular endothelial growth factor (VEGF) plays a major role in tumor angiogenesis. VEGF-C, however, is thought to stimulate the growth of lymphatic vessels because an expression of its specific receptor, VEGF receptor-3 (VEGFR-3), was demonstrated to be restricted to lymphatic vessels. Here we demonstrate that the inactivation of VEGFR-3 by a novel blocking monoclonal antibody (mAb) suppresses tumor growth by inhibiting the neo-angiogenesis of tumor-bearing tissues. Although VEGFR-3 is not expressed in adult blood vessels, it is induced in vascular endothelial cells of the tumor-bearing tissues. Hence, VEGFR-3 is another receptor tyrosine kinase involved in tumor-induced angiogenesis. Micro-hemorrhage in the tumor-bearing tissue was the most conspicuous histologic finding specific to AFL4 mAb-treated mice. Scanning microscopy demonstrated disruptions of the endothelial lining of the postcapillary venule, probably the cause of micro-hemorrhage and the subsequent collapse of the proximal vessels. These findings suggest the involvement of VEGFR-3 in maintaining the integrity of the endothelial lining during angiogenesis. Moreover, our results suggest that the VEGF-C/VEGFR-3 pathway may serve another candidate target for cancer therapy.

Role of the Vascular Endothelial Growth Factor Pathway in Tumor Growth and Angiogenesis

2005 ◽  
Vol 23 (5) ◽  
pp. 1011-1027 ◽  
Author(s):  
Daniel J. Hicklin ◽  
Lee M. Ellis
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Vegf Pathway ◽  
Endothelial Growth Factor

New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. Hence, the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research. The vascular endothelial growth factor (VEGF) pathway is well established as one of the key regulators of this process. The VEGF/VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities, cell-type expression, and function. Activation of the VEGF-receptor pathway triggers a network of signaling processes that promote endothelial cell growth, migration, and survival from pre-existing vasculature. In addition, VEGF mediates vessel permeability, and has been associated with malignant effusions. More recently, an important role for VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant sites of neovascularization. The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational design and development of agents that selectively target this pathway. Studies with various anti-VEGF/VEGF-receptor therapies have shown that these agents can potently inhibit angiogenesis and tumor growth in preclinical models. Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.

The Role of Vascular Endothelial Growth Factor in Tumor Angiogenesis

1998 ◽  
pp. 305-318
Author(s):  
Georg Breier ◽  
Annette Damert ◽  
Sabine Blum ◽  
Ernst Reichmann ◽  
Karl H. Plate ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tumor Angiogenesis ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor
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