Activation of the lymphotoxin beta receptor by cross-linking induces chemokine production and growth arrest in A375 melanoma cells.
The lymphotoxin beta receptor (LT beta R) was originally described as a transcribed sequence encoded on human chromosome 12p, with homology to the TNF receptor family. Subsequently, a recombinant LT beta R was shown to bind LT alpha LT beta heteromeric complexes. In this study, we have shown that LT beta R is expressed in a variety of tissues and cell lines of monocytic lineage, as well as in fibroblast and human melanoma cell lines. Unlike other members of the TNF receptor family, LT beta R is not expressed by peripheral blood T cells. A chimeric fusion protein consisting of the extracellular domain of LT beta R fused to the Fc region of human IgG1 was used to develop mAbs against LT beta R. Cross-linking LT beta R on A375 melanoma cells with these Abs generated an antiproliferative signal. In addition, the IL-8 and RANTES chemokines, early indicators of inflammation, were secreted by the A375 melanoma line and the WI38VA13 fibroblast line in response to cross-linking of LT beta R. These same activities could be induced by membrane-bound and soluble LT beta and LT alpha LT beta oligomers.
Degli-Esposti
M A
MA
Department of Biochemistry, Immunex Corporation, Seattle, WA 98101, USA.
Davis-Smith
T
T
Din
W S
WS
Smolak
P J
PJ
Goodwin
R G
RG
Smith
C A
CA
D000328:Adult; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D001704:Biopolymers; D018925:Chemokines / Q000096:biosynthesis*; D003432:Cross-Linking Reagents; D005333:Fetus; D006131:Growth Inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000096:biosynthesis; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D053308:Lymphotoxin-beta; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D012995:Solubility; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D001704:Biopolymers; D018925:Chemokines; D003432:Cross-Linking Reagents; D006131:Growth Inhibitors; D007141:Immunoglobulin Fc Fragments; C505886:LTB protein, human; C505697:LTBR protein, human; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor