Induction of "antigen silencing" in melanomas by oncostatin M: down-modulation of melanocyte antigen expression.
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.
Durda
Paul J
PJ
Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. pdurda@partners.org
Dunn
Ian S
IS
Rose
Lenora Boyle
LB
Butera
David
D
Benson
Elizabeth M
EM
Pandolfi
Franco
F
Kurnick
James T
JT
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
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