Angiogenesis in malignant lymphoma.
OBJECTIVE
Angiogenesis plays an important role in the pathophysiology of both solid tumors and hematologic malignancies. Angiogenesis-associated parameters are important prognosticators, and tumor blood vessels are an emerging target for therapy. This review addresses the evidence of the role of angiogenesis in malignant lymphoma and discusses some therapeutic implications.


RESULTS
In angiogenesis assays, lymphoma cells show angiogenic properties. Tumor vascularization is higher in lymphoma tissue than in reactive lymph nodes and increases in step with clinically more aggressive lymphoma subtypes and advanced-stage disease. High levels of vascular endothelial growth factor in blood and tissue are associated with adverse prognosis. Vascular endothelial growth factor and vascular endothelial growth factor receptors are also present in lymphoma cells. Therapy against vascular endothelial growth factor in animal models is effective and points to both the tumor cell and the host endothelium as targets. Structural microvessel abnormalities are present in some lymphoma subtypes. The role of angiogenesis might vary in lymphoma subtypes because the prognostic value of microvessel density and the expression of angiogenesis-related molecules differ between lymphoma subtypes. There are also differences in blood vessel phenotype between lymphoma subtypes. This heterogeneity may have implications for antiangiogenic therapies. Antiangiogenic therapy in human lymphoma is still in its infancy.


CONCLUSIONS
The role of angiogenesis in malignant lymphoma is evident. Tumor vasculature is an attractive target for lymphoma therapy. Differences between lymphoma subtypes must be taken into account in the selection of the most suitable patients for trials with antiangiogenic agents.
Koster
Ad
A
Department of Haematology, University Medical Centre Nijmegen, The Netherlands.
Raemaekers
John M M
JM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000503:physiopathology*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A