Galectin-1-mediated apoptosis in mycosis fungoides: the roles of CD7 and cell surface glycosylation.
Sezary cells, the malignant T cells in mycosis fungoides/Sezary syndrome, resist a variety of apoptosis-inducing agents, a feature that contributes to the poor response to therapy in mycosis fungoides. Galectin-1 is a mammalian lectin that triggers T cell apoptosis. For T cells to be susceptible to galectin-1-induced apoptosis, the T cells must express specific glycoprotein receptors, such as CD7, that bear the specific oligosaccharides recognized by galectin-1. Because Sezary cells are characteristically CD7(-), lack of CD7 expression has been proposed to render Sezary cells resistant to galectin-1-induced death. However, the role played by aberrant cell surface glycosylation in resistance of Sezary cells to galectin-1 has not been examined. In this study, we demonstrated abundant galectin-1 in mycosis fungoides skin lesions, indicating that Sezary cells are exposed to galectin-1 in vivo. To determine specific characteristics of Sezary cells that contribute to galectin-1 resistance, we assessed CD7 expression and cell surface glycosylation of Sezary cells in mycosis fungoides lesions and of four Sezary T cell lines. Sezary cells in primary lesions and Sezary T cell lines demonstrated a characteristic "glycotype" with sialylated core 1 O-glycans that promote galectin-1 resistance. Expression of CD7 was necessary but not sufficient for galectin-1-induced death of Sezary cell lines. In addition, CD7(-) Sezary cell lines, and Sezary cells within mycosis fungoides lesions, expressed galectin-1, whereas CD7-positive Sezary cell lines did not express galectin-1. We propose that both loss of CD7 expression and altered cellular glycosylation contribute to apoptosis resistance of malignant T cells in mycosis fungoides.
Roberts
Alice A
AA
Department of Pathology, UCLA School of Medicine, Los Angeles, California 90095-0657, USA.
Amano
Maho
M
Felten
Christopher
C
Galvan
Marisa
M
Sulur
Giri
G
Pinter-Brown
Lauren
L
Dobbeling
Udo
U
Burg
Gunter
G
Said
Jonathan
J
Baum
Linda G
LG
D019011:Antigens, CD7 / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D037483:Galectin 1 / Q000378:metabolism* / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D009182:Mycosis Fungoides / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D019011:Antigens, CD7; D037483:Galectin 1