Premium
Differential expression and tumor necrosis factor‐mediated regulation of TNFRSF 11b/osteoprotegerin production by human melanomas
Author(s) -
Oliver Janine L.,
Alexander Matthew P.,
Norrod Allison G.,
Mullins Irene M.,
Mullins David W.
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12091
Subject(s) - osteoprotegerin , tumor necrosis factor alpha , cancer research , osteoclast , receptor , rankl , medicine , tumor microenvironment , microbiology and biotechnology , immunology , biology , tumor cells , activator (genetics)
Summary Tumors escape host immune responses, in part, through the release of immunomodulatory factors and decoy receptors into their microenvironment. Several cancers express surface‐bound and soluble members of the tumor necrosis factor ( TNF ) receptor superfamily, including TNFRSF 11b/osteoprotegerin ( OPG ). In its physiologic role, OPG regulates bone remodeling through competition for osteoclast‐activating cytokines and protects newly forming bone from T cell‐mediated apoptosis. In multiple tumor types, OPG production is associated with an aggressive phenotype and increased metastasis to bone, but no study has examined OPG production in human metastatic melanoma. We demonstrate that a significant proportion of human metastatic melanomas constitutively produces OPG through a mechanism governed by membrane‐bound TNF ‐α signaling through TNF receptor 1 ( TNFR 1). These observations both define a specific mechanism that regulates melanoma production of OPG and establish a new molecular target for the therapeutic regulation of OPG .