UMLS:C0019829 - FACTA Search

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Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD30 antigen was originally described as a specific surface marker for Hodgkin's lymphoma. Recent work established CD30 as a member of the tumor necrosis factor/nerve growth factor receptor superfamily whose ligand (CD30L) has also been cloned and expressed; CD30L is active as membrane-bound type II glycoprotein. Here, CD30L mRNA expression was studied in a panel of 102 continuous human leukemia-lymphoma cell lines and was found only in four Burkitt lymphoma, one Burkit-type acute lymphoblastic leukemia and one non-Hodgkin's lymphoma (NHL) cell line. The product of CD30L mRNA is expressed as a membrane protein on the surface of these malignant B-cell lines. Treatment of these cell lines with soluble CD27L, phorbol ester or staphylococcus aureus Cowan antigen resulted in the enhancement of cell surface CD30L protein expression. CD30L mRNA was not detected in normal unstimulated peripheral blood (PB) monocytes, monocyte-derived macrophages, or T-cells, but was detected in primary granulocytes; exposure to activating reagents induced and upregulated CD30L transcription in these different PB populations. While CD40 and CD30L surface protein expression on PB monocytes could be enhanced or induced by treatment with gamma-interferon, these cells remained negative for CD30, both at the mRNA and at the protein level. Similarly, PB monocyte-derived macrophages and granulocytes remained negative for CD30 mRNA and protein expression, regardless of stimulation. Only activated T-cells expressed CD30 mRNA and surface protein. CD30L-transfected cells and cells constitutively expressing CD30L delivered a similar stimulus for proliferation of the CD30+ Hodgkin's disease (HD)-derived cell line HDLM-2, but inhibited proliferation of the CD30+ large cell anaplastic lymphoma cell line KARPAS-299. These data provide strong evidence for the involvement in growth regulation of recombinant and natural CD30L through its interaction with the CD30 receptor. Collectively, these data suggest that the CD30L-CD30 interaction has potent biological activity and might play a critical role in the immune response and pathogenesis of HD and some NHL, in particular Burkitt lymphomas.
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PMID:Expression and regulation of CD30 ligand and CD30 in human leukemia-lymphoma cell lines. 752 56

The CD30-activation marker was detected as the Hodgkin-associated Ki-I antigen and is regarded as a target for the treatment of Hodgkin patients with immunotoxins. The CD30 is released from tumor cells and this soluble CD30 (sCD30) is an indicator of the disease activity. Since the shedding of sCD30 may be influenced by antibodies, we produced 6 new CD30-specific antibodies (Ki-2 to Ki-7) for the purpose of finding antibodies that might inhibit the formation of sCD30. Ki-2 to Ki-7 and the other anti-CD30 antibodies Ki-I, Ber-H2, HeFi-I, M44, M67, HRS-I, HRS-4 and C10 were employed for epitope mapping. The binding of a particular radio-labeled anti-CD30 antibody to Hodgkin's-disease-derived L540 cells was completed by addition of the various non-labeled anti-CD30 antibodies. Three non-overlapping regions, expressing different antigen-specific determinants, could be defined on the extracellular part of the CD30 molecule. Cluster A of determinants was recognized by Ki-2, Ki-4, Ki-6 and Ki-7, Ber-H2, HRS-I and HRS-4, while cluster B was detected by Ki-I, Ki-5 and M67. Cluster C, which probably contains the binding site for the CD30 ligand, was defined by Ki-3, M44, HeFi-I and C10. Co-culture experiments of L540 cells with the various antibodies followed by the isolation of sCD30 from culture supernatant fluids revealed that the release of sCD30 was most strongly increased by Ki-I and weakly enhanced by Ki-2, Ki-3, Ki-5 and HeFi-I, whereas it was almost completely inhibited by Ki-4 and to a slightly lesser extent by Ber-H2.
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PMID:Shedding of the soluble form of CD30 from the Hodgkin-analogous cell line L540 is strongly inhibited by a new CD30-specific antibody (Ki-4). 753 Feb 38

The CD30 ligand (CD30L) and CD40L are members of the tumor necrosis factor (TNF) protein superfamily, CD30L and CD40L are mainly expressed as membrane-bound proteins by activated T cells. CD30L and CD40L are costimulatory for T cell proliferation and activation. Further, CD40L is a critical signal for T cell-dependent activation of B cells. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the neoplastic component of Hodgkin's disease (HD), express high levels of the counterreceptors CD30 and CD40. We have found that both the recombinant CD30L and CD40L enhanced interleukin (IL)-6, TNF and lymphotoxin (LT)-alpha release from cultured H-RS cells. In addition, CD40L, but not CD30L, induced IL-8 secretion. CD30L and CD40L seem to share some redundant biological activities involved in the deregulated secretion of cytokines known to play a central role in the clinical presentation and pathology of HD. Further, CD30L enhanced surface expression of intercellular adhesion molecule-1 (ICAM-1/CD54) on cultured H-RS cells, which is frequently overexpressed on primary H-RS cells. CD30L- and CD40L-enhanced CD54 surface expression is followed by elevated shedding of CD54, as shown by detection of elevated 82-kDa soluble (s) CD54 levels in culture supernatants after stimulation with both ligands. CD30L and CD40L share common pleiotropic biological activities on CD30+/CD40+ H-RS cells and are elements of the cytokine and cell contact-dependent activation network typical for HD, a tumor of cytokine producing cells.
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PMID:Recombinant CD30 ligand and CD40 ligand share common biological activities on Hodgkin and Reed-Sternberg cells. 762 81

CD30 is a member of the tumor necrosis factor receptor superfamily. CD30 was originally described as a cell surface antigen on primary and cultured Hodgkin's and Reed-Sternberg cells. In this study, recombinant human CD30 ligand was expressed on the surface of CV-1/EBNA cells and tested for biologic activities on a variety of different CD30+ human lymphoma cell lines. CD30 ligand enhanced Ig secretion of Epstein-Barr virus (EBV)-immortalized, CD30+ lymphoblastoid B-cell lines, but not Burkitt lymphoma lines. Recombinant CD30 ligand enhanced proliferation of "T-cell-like" Hodgkin's disease-derived cell lines and an adult T-cell leukemia cell line, but not "B-cell-like" Hodgkin's disease-derived cell lines, CD30+, EBV-immortalized lymphoblastoid B-cell lines, or CD30+ and EBV+ tumor B-cell non-Hodgkin's lymphoma cell lines. In addition, CD30 ligand mediated reduction of proliferation and viability, by induction of cytolytic cell death, of CD30+, large-cell anaplastic lymphoma cell lines. Two new antibodies, M44 and M67, against the CD30 antigen demonstrated similar biologic activities to the CD30 ligand. Taken together, these data demonstrate pleiotropic biologic activities of the CD30 ligand on different CD30+ lymphoma cell lines and indicate that the CD30-CD30 ligand interaction might have a pathophysiologic role in Hodgkin's and some non-Hodgkin's lymphomas.
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PMID:Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines. 816 76

The CD30 surface molecule is a recently identified member of the tumor necrosis factor/nerve growth factor receptor superfamily. Within the cytoplasmic signal transducing domain, CD30 shares no significant homology to other members of this family. Signaling events engaged via CD30 are still unknown. We here identify the NF-kappabeta transcription factor as a target of the CD30-induced signal pathway in Hodgkin's disease (HD) cells. Exposure of HD cells to CD30 ligand induces release of interleukin-6 (IL-6) that can be duplicated by cross-linking HD-cells to an agonistic anti-CD30 specific monoclonal antibody (alphaCD30), but not by cross-linking to an isotype-identical irrelevant monoclonal antibody. Cross-linking of HD cells to alphaCD30 leads to enhanced accumulation of IL-6 mRNA in a time-dependent fashion resulting from transcriptional activation of the IL-6 promoter. Transient transfection assays using a series of deleted IL-6 promoter constructs linked to the human growth hormone gene as a reporter gene furthermore indicate that transcriptional activation of the IL-6 promoter requires the presence of an intact NF-kappabeta binding site. In addition, introduction of an NF-kappabeta binding site appeared to be sufficient to confer inducibility of an heterologous promoter on activation of CD30 in HD cells. Cross-linking of CD30 promotes rapid and transient binding activity of nuclear proteins to the NF-kappabeta recognition site of the IL-6 promoter. Supershift experiments using a series of monoclonal antibodies recognizing distinct members of the NF-kappaBeta transcription factor family furthermore indicate that in CD30 cross-linked HD cells p50, p65/Rel-A, and Rel-B are present, whereas the c-rel protein is not.
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PMID:Activation of Hodgkin cells via the CD30 receptor induces autocrine secretion of interleukin-6 engaging the NF-kappabeta transcription factor. 1101 49

The membrane-bound proteins CD30 ligand (CD30L), CD40L and 4-1BBL are members of the tumor necrosis factor (TNF) superfamily. They are expressed mainly by activated T cells. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, regarded as the malignant components of Hodgkin's disease (HD), display high levels of the counter-receptors for these ligands, ie CD30, CD40 and 4-1BB. CD30L and CD40L are known to share some biological activities that can be linked to the unbalanced secretion of cytokines seen in HD. In addition, cell contact-dependent molecules such as adhesion or activation antigens are critically involved in T cell/H-RS cell interactions. Primary and cultured H-RS cells frequently overexpress intercellular adhesion molecule-1 (ICAM-1/CD54), BB-1 (B7-1/CD80) and B70/B7-2 (CD86). Here we show that CD30L and CD40L, but not 4-1BBL upregulate CD54 expression by cultured H-RS cells on the mRNA and protein level, as a result of transcriptional gene activation. Furthermore, enhanced CD54 surface expression by these cells is accompanied by increased shedding of surface-bound CD54, as evidenced by high levels of the 82 kDa soluble (s) CD54 form detectable in culture supernatants after specific stimulation. Addition of CD30L in combination with CD40L to cultured H-RS cells additively enhanced CD54 surface expression and its shedding. These results may give a plausible explanation why sCD54 serum levels are increased in patients with HD.
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PMID:The CD30 ligand and CD40 ligand regulate CD54 surface expression and release of its soluble form by cultured Hodgkin and Reed-Sternberg cells. 865 79

The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.
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PMID:CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues. 870 86

Hodgkin disease (HD) is characterized by the presence of a small number (usually <1% of total tumor mass) of the typical Hodgkin and Reed-Sternberg (H-RS) cells in a hyperplastic background of normal reactive lymphocytes, plasma cells, histiocytes, neutrophils, eosinophils, and stromal cells. HRS cells produce various cytokines, growth factors, and express cytokine receptors and activation antigens, implying a predominant role for these molecules in the pathophysiology of Hodgkin disease. HD may therefore be regarded as a tumor of cytokine producing cells. The CD30 antigen has been characterized as a marker for cultured and primary Hodgkin and Reed-Sternberg cells, and was found to be overexpressed in Hodgkin disease and a subgroup of non-Hodgkin lymphomas including large cell anaplastic lymphomas and Burkitt lymphomas. The molecular cloning of the CD30 antigen revealed that CD30 is a member of the tumor necrosis factor/nerve growth factor receptor superfamily. The cloning of the cognate for CD30, currently termed CD30 ligand, confirmed that the CD30 antigen functions as a cytokine receptor. Recombinant CD30 ligand is a membrane-bound protein with pleiotropic biological activities for different CD30+ lymphoma types, but also for the immune system, mainly T cells. CD30L belongs to the emerging tumor necrosis factor ligand superfamily. The CD30-CD30 ligand interaction could have a critical pathophysiological role in malignant lymphomas, particularly Hodgkin disease, large cell anaplastic lymphomas and Burkitt lymphomas, and is also involved in activation and functioning of the T cell-dependent immune system.
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PMID:CD30 ligand, a member of the TNF ligand superfamily, with growth and activation control CD30+ lymphoid and lymphoma cells. 883 95

The presence of a prominent tissue eosinophilia represents a typical histopathologic hallmark of Hodgkin's disease (HD). To evaluate the putative role of eosinophils on tumor cell regulation in HD, we have analyzed these cells for the functional expression of CD30 ligand (CD30L), a surface molecule able to transduce CD30-mediated proliferation signals on Hodgkin's (H) and Reed-Sternberg (RS) cells. The results demonstrate that circulating and tissue eosinophils from normal donors and patients with HD or hypereosinophilic syndrome (HES), display CD30L mRNA and express CD30L protein, as shown by immunostaining with a specific monoclonal antibody (M80) and with a biotinylated soluble CD30-Fc fusion protein. The surface density of CD30L on eosinophils from HD and HES patients was remarkably higher compared with healthy donors, probably reflecting a cytokine-mediated upregulation in these pathologic conditions. Accordingly, we provide evidence that cytokines regulating eosinophils proliferation and activation, ie, interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF), are able to enhance the cellular density of CD30L on purified eosinophils from normal subjects. Finally, we show that native CD30L on human eosinophils is a functionally active surface structure able to transduce proliferative signals on CD30+ target cells, including cultured H-RS cells. Our data suggest that eosinophils may not merely represent innocent bystanders, but rather act as important elements in the pathology of HD by contributing to the deregulated network of CD30/CD30L-mediated interactive signals between H-RS cells and surrounding reactive cells.
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PMID:Human eosinophils express functional CD30 ligand and stimulate proliferation of a Hodgkin's disease cell line. 889 93

CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30. Although several lines of evidence indicate that CD30L plays a key role as a paracrine- or autocrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic significance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the anti-CD30L monoclonal antibody M80, we were able to show that human hematopoietic malignancies of different lineage and maturation stage display a frequent and broad expression of the ligand. CD30L mRNA and surface protein were detected in 60% of acute myeloid leukemias (AMLs), 54% of B-lineage acute lymphoblastic leukemias (ALLs), and in a consistent fraction (68%) of B-cell lymphoproliferative disorders. In this latter group, hairy cell leukemia and high-grade B-cell non-Hodgkin's lymphoma (B-NHL) expressed a higher surface density of CD30L as compared with B-cell chronic lymphocytic leukemia and low-grade B-NHL. Purified plasmacells from a fraction of multiple myeloma patients also displayed CD30L mRNA and protein. A more restricted expression of CD30L was found in T-cell tumors that was mainly confined to neoplasms with an activated peripheral T-cell phenotype, such as T-cell prolymphocytic leukemia, peripheral T-NHL, and adult T-cell leukemia/lymphoma. In contrast, none of the T-lineage ALLs analyzed expressed the ligand. In AML, a high cellular density of CD30L was detected in French-American-British M3, M4, and M5 phenotypes, which are directly associated with the presence on tumor cells of certain surface structures, including the p55 interleukin-2 receptor alpha-chain, the alpha(M) (CD11b) chain of beta2 integrins, and the intercellular adhesion molecule-1 (CD54). Analysis of normal hematopoietic cells evidenced that, in addition to circulating and tonsil B cells, a fraction of bone marrow myeloid precursors, erythroblasts, and subsets of megakaryocytes also express CD30L. Finally, we have shown that native CD30L expressed on primary leukemic cells is functionally active by triggering both mitogenic and antiproliferative signals on CD30+ target cells. As opposed to CD30L, only 10 of 181 primary tumors expressed CD30 mRNA or protein, rendering therefore unlikely a CD30-CD30L autocrine loop in human hematopoietic neoplasms. Taken together, our data indicate that CD30L is widely expressed from early to late stages of human hematopoiesis and suggest a regulatory role for this molecule in the interactions of normal and malignant hematopoietic cells with CD30+ immune effectors and/or microenvironmental accessory cells.
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PMID:CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin. 905 27

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