| Malignant cells cultured in three-dimensional (3D) models have been found to be
phenotypically and biochemically different from their counterparts cultured conventionally. Since
most of these studies employed solid tumor types, how 3D culture affects multiple myeloma (MM)
cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture
model with those in conventional culture. While the conventionally cultured cells were present in
single cells or small clusters, MM-3D cells grew in large spheroids. We discovered that STAT3 was the
pathway that was more activated in 3D in both cell lines. The active form of STAT3 (phospho-STAT3
or pSTAT3), which was absent in MM cells cultured conventionally, became detectable after 1–2 days
in 3D culture. This elevated pSTAT3 level was dependent on the 3D environment, since it disappeared
after transferring to conventional culture. STAT3 inhibition using a pharmacological agent, Stattic,
significantly decreased the cell viability of MM cells and sensitized them to bortezomib in 3D culture.
Using an oligonucleotide array, we found that 3D culture significantly increased the expression
of several known STAT3 downstream genes implicated in oncogenesis. Since most primary MM
tumors are naturally STAT3-active, studies of MM in 3D culture can generate results that are more
representative of the disease. |