title: Induction of "antigen silencing" in melanomas by oncostatin M: down-modulation of melanocyte antigen expression.
abstract: We previously reported that antigen expression in melanoma cell lines is down-regulated by proteins secreted by antigen-negative melanoma cells. Here we report the purification and characterization of one of these down-regulatory factors, the cytokine, oncostatin M (OSM), which transmits its signal via the gp130 cell surface receptor, resulting in the selective down-modulation of the melanocyte lineage antigens: Melan-A/MART-1, gp100, tyrosinase, tyrosinase-related proteins 1 and 2, and the M isoform of microphthalmia transcription factor. Furthermore, we have found that some melanoma cell lines produce as yet uncharacterized factors distinct from OSM which also down-modulate antigen expression via signaling pathways different from that employed by OSM. These data indicate that there may be several regulatory pathways and molecules involved in the antigen-silencing process which may be related to the state of differentiation of the tumor cell and may affect the outcome of antitumor vaccine immunotherapies.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. pdurda@partners.org
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Durda
authors.forename: Ian S
authors.initials: IS
authors.lastname: Dunn
authors.forename: Lenora Boyle
authors.initials: LB
authors.lastname: Rose
authors.forename: David
authors.initials: D
authors.lastname: Butera
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Benson
authors.forename: Franco
authors.initials: F
authors.lastname: Pandolfi
authors.forename: James T
authors.initials: JT
authors.lastname: Kurnick
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D015536:Down-Regulation; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053683:Oncostatin M; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D053677:Receptors, Oncostatin M
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D053683:Oncostatin M