AI Article Synopsis
- Dexamethasone is commonly used to treat multiple myeloma, but resistance to the drug is a significant clinical challenge.
- CD44 is identified as an adhesion molecule that helps multiple myeloma cells survive by interacting with hyaluronan, which is linked to increased resistance to Dexamethasone.
- Engaging CD44 with antibodies or hyaluronan can protect myeloma cells from the growth-inhibiting effects of Dexamethasone, suggesting that targeting CD44 may be a strategy to overcome drug resistance.
Article 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 IkappaB-alpha, 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.
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| http://dx.doi.org/10.1111/j.1600-0609.2007.01014.x | DOI Listing |
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