Halting angiogenesis suppresses carcinoma cell invasion.
The importance of angiogenesis in malignant tumor growth has been interpreted mainly in terms of oxygen and nutrient supply. Here we demonstrate its fundamental role for tumor invasion of malignant human keratinocytes in surface transplants on nude mice. Distinct patterns of angiogenesis and vascular endothelial growth factor receptor-2 (VEGFR-2) expression allowed us to distinguish between benign and malignant cells. Functional inactivation of VEGF-R2 by a blocking antibody disrupted ongoing angiogenesis and prevented invasion of malignant cells, without reducing tumor cell proliferation. The reversion of a malignant into a benign phenotype by halting angiogenesis demonstrates a significant function of vascular endothelium for tumor invasion.
Skobe
M
M
Division of Carcinogenesis and Differentiation, German Cancer Research Center (DKFZ), Heidelberg.
Rockwell
P
P
Goldstein
N
N
Vosseler
S
S
Fusenig
N E
NE
D000818:Animals; D002471:Cell Transformation, Neoplastic; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D017403:In Situ Hybridization; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000150:complications*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D011975:Receptors, Mitogen / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor