Progression of lymphomatoid papulosis to systemic lymphoma is associated with escape from growth inhibition by transforming growth factor-beta and CD30 ligand.
Our objective is to understand the mechanism of progression of lymphomatoid papulosis (LyP) to CD30+ systemic lymphoma. LyP lesions appear in recurrent crops that regress, only to reappear at a later date in the same or different locations. About 10% of patients develop systemic lymphoma. Because transforming growth factor-beta (TGF-beta) and CD30 ligand inhibit the growth of normal lymphocytes and can be detected in regressing lesions of LyP, we tested the effect of these cytokines on cell lines clonally derived from LyP in the progression to systemic lymphoma. TGF-beta failed to inhibit the growth of lymphoma cells from advanced disease due to mutations of the TGF-beta receptor complex that prevented binding of the ligand to tumor cells. A CD30 ligand agonist antibody caused proliferation of tumor cells from one patient and had no effect on tumor cells of another. In contrast, a Fas agonist antibody caused significant growth inhibition of all cell lines. The results suggest that progression of LyP to lymphoma is associated with escape of lymphoma cells from growth regulation by TGF-beta and CD30 ligand.
Kadin
M E
ME
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA. mkadin@caregroup.harvard.edu
Levi
E
E
Kempf
W
W
D000906:Antibodies / Q000276:immunology; D053285:CD30 Ligand; D002455:Cell Division; D004247:DNA / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D017730:Ki-1 Antigen / Q000235:genetics / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D017731:Lymphomatoid Papulosis / Q000150:complications* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D000906:Antibodies; D053285:CD30 Ligand; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; C505774:TNFSF8 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004247:DNA