Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL
| Autor: | Jane A. Gross, Weifeng Xu, Paul A. Santini, Eric Sievers, Stacey R. Dillon, Amy Chadburn, Xugang Qiao, Elizabeth Hyjek, Daniel M. Knowles, Joong-won Lee, Andrea Cerutti, Bing He, April Chiu, Ethel Cesarman |
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| Rok vydání: | 2006 |
| Předmět: |
Cell Survival
Transmembrane Activator and CAML Interactor Protein Tumor Necrosis Factor Ligand Superfamily Member 13 Immunology Biology Biochemistry Immunophenotyping Paracrine signalling stomatognathic system immune system diseases Cell Line Tumor hemic and lymphatic diseases B-Cell Activating Factor medicine Humans B-Cell Maturation Antigen skin and connective tissue diseases B-cell activating factor Receptor Autocrine signalling Cell Proliferation B-Lymphocytes Neoplasia Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Germinal center Cell Biology Hematology medicine.disease Hodgkin Disease Lymphoma stomatognathic diseases Cancer research RNA Interference Signal transduction Signal Transduction |
| Zdroj: | Blood. 109:729-739 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2006-04-015958 |
| Popis: | Hodgkin lymphoma (HL) originates from the clonal expansion of malignant Hodgkin and Reed-Sternberg (HRS) cells. These B-cell–derived elements constitute less than 10% of the tumoral mass. The remaining tissue is comprised of an inflammatory infiltrate that includes myeloid cells. Myeloid cells activate B cells by producing BAFF and APRIL, which engage TACI, BCMA, and BAFF-R receptors on the B cells. Here, we studied the role of BAFF and APRIL in HL. Inflammatory and HRS cells from HL tumors expressed BAFF and APRIL. Unlike their putative germinal center B-cell precursors, HRS cells lacked BAFF-R, but expressed TACI and BCMA, a phenotype similar to that of plasmacytoid B cells. BAFF and APRIL enhanced HRS cell survival and proliferation by delivering nonredundant signals via TACI and BCMA receptors through both autocrine and paracrine pathways. These signals caused NF-κB activation; Bcl-2, Bcl-xL, and c-Myc up-regulation; and Bax down-regulation, and were amplified by APRIL-binding proteoglycans on HRS cells. Interruption of BAFF and APRIL signaling by TACI-Ig decoy receptor, which binds to and neutralizes BAFF and APRIL, or by small-interfering RNAs targeting BAFF, APRIL, TACI, and BCMA inhibited HRS cell accumulation in vitro and might attenuate HL expansion in vivo. |
| Databáze: | OpenAIRE |
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