Proliferation of CD30+ T-helper 2 lymphoma cells can be inhibited by CD30 receptor cross-linking with recombinant CD30 ligand.

Abstract

PURPOSE:

Cutaneous anaplastic large cell lymphomas (ALCLs) are characterized by the expression of CD30, spontaneous regression of skin lesions, and increased concentration of CD30 ligand (CD30L). We hypothesize that CD30-CD30L interactions explain the unusual clinical behavior of cutaneous ALCLs.

EXPERIMENTAL DESIGN:

Eight lymphoma cell lines established from four different patients were analyzed for T-cell clonality using PCR and subsequently denaturating gradient gel electrophoresis. The expression levels of CD30 were assessed by flow cytometry. Secreted cytokines [IFN-gamma, interleukin (IL)-2, IL-4, IL-6, IL-8, and IL-10] were determined in the supernatant after 3-day culture. Proliferation and apoptosis of cultured cells were measured by 5-bromo-2-desoxyuridine and propidium iodine incorporation.

RESULTS:

The results showed different levels of CD30 expression and a predominant T-helper 2 profile. In a cell kinetic analysis we found that ALCL cell growth is effectively inhibited by CD30L but only in those cell lines expressing CD30 molecules in sufficient amounts on the cell surface. Cell cycle analysis revealed that growth regulation was because of apoptosis and growth arrest, and was dependent on cell culture conditions. Comparison of effects of ligation with CD30L and anti-CD30 agonistic antibody HeFi-1 revealed higher efficacy for CD30L in these ALCL lines.

CONCLUSIONS:

CD30+ ALCL cells can be growth inhibited by receptor ligation. Observed pleiotropic effects of CD30 signaling are most likely dependent on cell cycle status and signal strength. The binding of CD30 by its ligand provides new opportunities for controlling cell growth and treatment of CD30+ ALCL.

• Authors: Jörg Willers, Reinhard Dummer, Werner Kempf, Thomas Kündig, Günter Burg, Marshall E Kadin
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 7 Pg. 2744-54 (Jul 2003) ISSN: 1078-0432 [Print] United States
• PMID: 12855655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CD30 Ligand
• Cytokines
• Ki-1 Antigen
• Membrane Glycoproteins
• Receptors, Antigen, T-Cell, gamma-delta
• TNFSF8 protein, human
• Propidium
• DNA
• Bromodeoxyuridine

Topics

• Apoptosis
• Bromodeoxyuridine (pharmacology)
• CD30 Ligand
• Cell Cycle
• Cell Division
• Cell Line, Tumor
• Cell Membrane (metabolism)
• Cytokines (metabolism)
• DNA (metabolism)
• Flow Cytometry
• Humans
• Ki-1 Antigen (biosynthesis)
• Kinetics
• Membrane Glycoproteins (metabolism)
• Polymerase Chain Reaction
• Propidium (pharmacology)
• Protein Binding
• Receptors, Antigen, T-Cell, gamma-delta (metabolism)
• Signal Transduction
• Th2 Cells (metabolism)
• Time Factors