Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia
Autor: | Janet Matthews, Catherine Durance, Elena Hoxha, John G. Gribben, Aine McCarthy, Andrew Clear, Li Jia, Feng-Ting Liu, Sameena Iqbal, Nadiha Uddin |
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Rok vydání: | 2014 |
Předmět: |
endocrine system diseases
Cellular differentiation Chronic lymphocytic leukemia Immunology Blotting Western Plasma Cells Receptor for Advanced Glycation End Products Fluorescent Antibody Technique chemical and pharmacologic phenomena Enzyme-Linked Immunosorbent Assay HMGB1 Biochemistry RAGE (receptor) immune system diseases hemic and lymphatic diseases medicine Tumor Cells Cultured Tumor Microenvironment Humans Immunoprecipitation HMGB1 Protein Cell Proliferation Tumor microenvironment Innate immune system Lymphoid Neoplasia biology TLR9 Cell Differentiation Cell Biology Hematology medicine.disease Flow Cytometry Prognosis Leukemia Lymphocytic Chronic B-Cell Coculture Techniques Survival Rate Tissue Array Analysis Case-Control Studies Culture Media Conditioned Toll-Like Receptor 9 Cancer research biology.protein cardiovascular system Lymph Nodes Signal transduction Neoplasm Recurrence Local Follow-Up Studies Signal Transduction |
Zdroj: | Blood. 123(11) |
ISSN: | 1528-0020 |
Popis: | Chronic lymphocytic leukemia (CLL) is a disease of an accumulation of mature B cells that are highly dependent on the microenvironment for maintenance and expansion. However, little is known regarding the mechanisms whereby CLL cells create their favorable microenvironment for survival. High-mobility group protein B-1 (HMGB1) is a highly conserved nuclear protein that can be actively secreted by innate immune cells and passively released by injured or dying cells. We found significantly increased HMGB1 levels in the plasma of CLL patients compared with healthy controls, and HMGB1 concentration is associated with absolute lymphocyte count. We therefore sought to determine potential roles of HMGB1 in modulating the CLL microenvironment. CLL cells passively released HMGB1, and the timing and concentrations of HMGB1 in the medium were associated with differentiation of nurse-like cells (NLCs). Higher CD68 expression in CLL lymph nodes, one of the markers for NLCs, was associated with shorter overall survival of CLL patients. HMGB1-mediated NLC differentiation involved internalization of both receptor for advanced glycation end products (RAGE) and Toll-like receptor-9 (TLR9). Differentiation of NLCs can be prevented by blocking the HMGB1-RAGE-TLR9 pathway. In conclusion, this study demonstrates for the first time that CLL cells might modulate their microenvironment by releasing HMGB1. |
Databáze: | OpenAIRE |
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