Abolished angiogenicity and tumorigenicity of Burkitt lymphoma by interleukin-10.
Because of its immunosuppressive properties, interleukin-10 (IL-10) is thought to play an important role in a number of human disease states, including inflammation, autoimmunity, and transplant rejection. In this study, we demonstrate that introduction of human or viral IL-10 genes into Burkitt's lymphoma cells markedly reduced their ability to grow as subcutaneous (sc) tumors in SCID mice. In vivo assays for angiogenesis revealed an inhibition of the angiogenic capacity of the IL-10-transfected lines. Recombinant human IL-10 abolished and viral IL-10 reduced vascular endothelial growth factor (VEGF)-165-induced neovascularization. Furthermore, IL-10 blocked the VEGF- and fibroblast growth factor (FGF)-2-induced proliferation of microvascular endothelial cells in vitro. The current observations suggest a direct role for IL-10 in the prevention of angiogenesis in human lymphoid malignancies.
Cervenak
L
L
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Morbidelli
L
L
Donati
D
D
Donnini
S
S
Kambayashi
T
T
Wilson
J L
JL
Axelson
H
H
Castaños-Velez
E
E
Ljunggren
H G
HG
Malefyt
R D
RD
Granger
H J
HJ
Ziche
M
M
Bejarano
M T
MT
D000818:Animals; D002051:Burkitt Lymphoma / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D002455:Cell Division; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression; D016753:Interleukin-10 / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D016753:Interleukin-10