Abstract
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.
Highlights
Studies of malignant cells using three-dimensional (3D) culture systems are believed to provide information that is more representative of the ‘real-life’ in vivo conditions, as opposed to those using cells cultured conventionally in monolayer or cell suspension
We have identified a good number of studies employing various 3D models to study cancer biology, with the majority of these studies focusing on malignant epithelial cells and neurogenic cells
We have found that the phosphorylated form of STAT3 (pSTAT3) nuclear staining was present in the vast majority of cells in the 3D culture, confirming that the elevated STAT3 activity is generalized phenomenon and not restricted to a small cell population
Summary
Studies of malignant cells using three-dimensional (3D) culture systems are believed to provide information that is more representative of the ‘real-life’ in vivo conditions, as opposed to those using cells cultured conventionally in monolayer or cell suspension. Cancers 2018, 10, 206 cells cultured in 3D have been shown to display substantial differences in their growth characteristics, gene expression and drug resistance patterns when compared to cells cultured conventionally [1,2,3]. Studies of malignant hematopoietic cells using 3D culture models are relatively scarce, and the impact of 3D culture on these cancer cells is incompletely understood. Multiple myeloma (MM), characterized by the accumulation of clonal malignant plasma cells in the three-dimensional bone marrow niches, represents 10% of all hematologic malignancies [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
