EMD originates from hyaluronan-induced homophilic interactions of CD44 variant-expressing MM cells under shear stress.

ABSTRACT: Extramedullary disease (EMD) is known to be associated with chemoresistance and poor prognosis in multiple myeloma (MM); however, the mechanisms of its development are not fully understood. Elucidating the mechanism of EMD development and its therapeutic targeting would greatly contribute to further improvement of treatment outcome in patients with MM. Here, we show that bone marrow stroma cell-derived hyaluronan (HA) elicits homophilic interactions of MM cells by binding to surface CD44, especially long-stretch variants, under physiological shear stress and generates cell clusters that might develop into EMD. We recapitulated the development of EMD via administration of HA in a syngeneic murine MM model in a CD44-dependent manner. HA-induced MM cell clusters exhibited the specific resista

SUBMITTER: Kikuchi J 

PROVIDER: S-EPMC9979770 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature