Lymphotoxin-beta receptor immune interaction promotes tumor growth by inducing angiogenesis.
Growth of solid fibrosarcoma tumors in mice was inhibited by the release of a solublelymphotoxin-beta receptor inhibitor (LTbetaR-immunoglobulin fusion protein) from the tumor cells. Tumor growth arrest in mice deficient in the ligand LTalpha1beta2 demonstrated the requirement for activation of the LTbetaR on the tumor cells by host cell-derived LTalpha1beta2. Activation of the LTbetaR resulted in enhanced release of macrophage inflammatory protein-2. Blocked angiogenesis was revealed in LTbetaR inhibitor-producing tumor nodules by immunohistochemistry and in vivo microscopy. The growth arrest of LTbetaR inhibitor-producing fibrosarcomas was overcome by forced MIP-2 expression in the tumor cells. Thus, LTbetaR activation on tumor cells by activated host lymphocytes can initiate a novel proangiogenic pathway leading to organized tumor tissue development.
Hehlgans
Thomas
T
Department of Pathology/Tumor Immunology, University of Regensburg, D-93042 Regensburg, Germany.
Stoelcker
Benjamin
B
Stopfer
Peter
P
Müller
Peter
P
Cernaianu
Grigore
G
Guba
Markus
M
Steinbauer
Markus
M
Nedospasov
Sergei A
SA
Pfeffer
Klaus
K
Männel
Daniela N
DN
D000818:Animals; D002455:Cell Division / Q000276:immunology / Q000502:physiology; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply* / Q000276:immunology / Q000473:pathology; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
C505887:Ltb protein, mouse; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins