Systemic dysregulation of CEACAM1 in melanoma patients.
It was previously shown that CEACAM1 on melanoma cells strongly predicts poor outcome. Here, we show a statistically significant increase of serum CEACAM1 in 64 active melanoma patients, as compared to 48 patients with no evidence of disease and 37 healthy donors. Among active patients, higher serum CEACAM1 correlated with LDH values and with decreased survival. Multivariate analysis with neutralization of LDH showed that increased serum CEACAM1 carries a hazard ratio of 2.40. In vitro, soluble CEACAM1 was derived from CEACAM1(+), but neither from CEACAM1(-) melanoma cells nor from CEACAM1(+) lymphocytes, and directly correlated with the number of CEACAM1(+) melanoma cells. Production of soluble CEACAM1 depended on intact de novo protein synthesis and secretion machineries, but not on metalloproteinase function. An unusually high percentage of CEACAM1(+) circulating NK and T lymphocytes was demonstrated in melanoma patients. CEACAM1 inhibited killing activity in functional assays. CEACAM1 expression could not be induced on lymphocytes by serum from patients with high CEACAM1 expression. Further, expression of other NK receptors was impaired, which collectively indicate on a general abnormality. In conclusion, the systemic dysregulation of CEACAM1 in melanoma patients further denotes the role of CEACAM1 in melanoma and may provide a basis for new tumor monitoring and prognostic platforms.
Markel
Gal
G
The Ella Institute for Melanoma Research and Treatment, Sheba Cancer Research Center, Sheba Medical Center, 52621 Tel Hashomer, Israel. markel@post.tau.ac.il
Ortenberg
Rona
R
Seidman
Rachel
R
Sapoznik
Sivan
S
Koren-Morag
Nira
N
Besser
Michal J
MJ
Bar
Jair
J
Shapira
Ronnie
R
Kubi
Adva
A
Nardini
Gil
G
Tessone
Ariel
A
Treves
Avraham J
AJ
Winkler
Eyal
E
Orenstein
Arie
A
Schachter
Jacob
J
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood* / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000276:immunology*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000276:immunology*; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D012878:Skin Neoplasms / Q000097:blood* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C112260:NCR1 protein, human; C431710:NCR3 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D017452:Receptors, IgG