Activation of the Lymphotoxin β Receptor by Cross-Linking Induces Chemokine Production and Growth Arrest in A375 Melanoma Cells

The lymphotoxin β receptor (LTβR) was originally described as a transcribed sequence encoded on human chromosome 12p, with homology to the TNF receptor family. Subsequently, a recombinant LTβR was shown to bind LTαLTβ heteromeric complexes. In this study, we have shown that LTβR 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, LTβR is not expressed by peripheral blood T cells. A chimeric fusion protein consisting of the extracellular domain of LTβR fused to the Fc region of human IgG1 was used to develop mAbs against LTβR. Cross-linking LTβR 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 W138VA13 fibroblast line in response to cross-linking of LTβR. These same activities could be induced by membrane-bound and soluble LTβ and LTαLTβ oligomers.