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
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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