During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium.
Localization of activated natural killer (A-NK) cells in the microvasculature of growing tumors is the result of recognition of the intracellular and vascular cell-adhesion molecules ICAM-1 and VCAM-1 on the tumor endothelium, mediated by lymphocyte function-associated protein LFA-1 and vascular lymphocyte function-associated protein VLA-4. In vitro and in vivo studies of A-NK cell adhesion to endothelial cells showed that vascular endothelial growth factor (VEGF) promotes adhesion, whereas basic fibroblast growth factor (bFGF) inhibits adhesion through the regulation of these molecules on tumor vasculature. Thus, some angiogenic factors may facilitate lymphocyte recognition of angiogenic vessels, whereas others may provide such vessels with a mechanism that protects them from cytotoxic lymphocytes.
Melder
R J
RJ
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114, USA.
Koenig
G C
GC
Witwer
B P
BP
Safabakhsh
N
N
Munn
L L
LL
Jain
R K
RK
D000818:Animals; D002448:Cell Adhesion; D019040:E-Selectin / Q000502:physiology; D016228:Endothelial Growth Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000276:immunology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000209:etiology / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000276:immunology*; D019007:P-Selectin / Q000502:physiology; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D019040:E-Selectin; D016228:Endothelial Growth Factors; D016169:Lymphocyte Function-Associated Antigen-1; D008222:Lymphokines; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1