Loss of receptors for transforming growth factor beta in human T-cell malignancies.
Ki-1 (CD30)+ cutaneous T-cell lymphomas CTCLs) are slowly progressive lymphomas in which initial spontaneous regression is often observed. To better understand the mechanisms of spontaneous regression and eventual tumor progression in Ki-1+ CTCLs, type beta transforming growth factor (TGF-beta)-mediated growth inhibition of clonally related cell lines derived from two time points, before and after tumor progression, was studied. TGF-beta 1 inhibited colony-forming efficiency (CFE) of a cell line (Mac-1) derived from clinically indolent Ki-1+ CTCLs but failed to inhibit CFE of Mac-2A and -2B cell lines from advanced CTCLs. To determine the basis for TGF-beta 1 resistance in advanced CTCL cells, we looked for possible defects in the expression of cell surface TGF-beta receptors. Mac-1 cells were found to express TGF-beta receptors I and II, which mediate growth inhibition, and the TGF-beta-binding proteoglycan betaglycan. In contrast, receptors I and II were not detected in CTCL lines Mac-2A and -2B even though these cell lines did express betaglycan. Various treatments that unmask or induce TGF-beta receptors in other cells failed to show evidence for these receptors in advanced CTCL cells. Loss of TGF-beta receptor expression in these cells correlated with a marked decrease in TGF-beta receptor II mRNA levels. Loss of cell surface TGF-beta receptors was also found in two of five other patients with T-cell lymphomas including the Sezary syndrome and a noncutaneous T-cell lymphoma, suggesting that loss of TGF-beta receptor expression may be a recurrent feature of human T-cell malignancies.
Department of Pathology, Beth Israel Hospital, Boston, MA 02215.
M E
ME
Kadin
M W
MW
Cavaille-Coll
R
R
Gertz
J
J
Massagué
S
S
Cheifetz
D
D
George
D000328:Adult; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D006801:Humans; D016399:Lymphoma, T-Cell / Q000276:immunology*; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D012751:Sezary Syndrome / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D018125:Receptors, Transforming Growth Factor beta