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CD44 and hyaluronan engagement promotes dexamethasone resistance in human myeloma cells
Author(s) -
Ohwada Chikako,
Nakaseko Chiaki,
Koizumi Masayuki,
Takeuchi Masahiro,
Ozawa Shinichi,
Naito Megumi,
Tanaka Hiroaki,
Oda Kayo,
Cho Ryuko,
Nishimura Miki,
Saito Yasushi
Publication year - 2008
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2007.01014.x
Subject(s) - cd44 , population , extracellular matrix , monoclonal antibody , cancer research , cell adhesion , cell culture , cell adhesion molecule , microbiology and biotechnology , biology , cell , chemistry , immunology , medicine , antibody , biochemistry , genetics , environmental health
Abstract Dexamethasone (Dex) is an effective therapeutic agent against multiple myeloma (MM); however, resistance to it often becomes a clinical issue. CD44 is an adhesion molecule that serves as a cell surface receptor for extracellular matrix components, including hyaluronan (HA). HA is an extracellular matrix component that is involved in survival and progression in MM. In the present report, we describe isolation of a CD44‐expressing population from a Dex‐sensitive MM cell line, RPMI8226, in which the CD44‐high population had a significantly higher potential to resist Dex than did the CD44‐low population. Furthermore, we demonstrate that CD44 engagement by an anti‐CD44 monoclonal antibody (mAb) or HA protects MM cells from Dex‐induced growth inhibition. The activity of HA was partially inhibited by blocking its binding to CD44, indicating that CD44 mediates HA activity promoting MM cell survival. CD44 engagement by an anti‐CD44 mAb led to phosphorylation and degradation of IκB‐α, thus preventing its Dex‐induced up‐regulation. Our data suggest that CD44 is not only an important mediator for the survival activity of HA, but it may also contribute to MM cell resistance to Dex.