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Updated: Apr 27, 2026

Analysis of Side Population in Solid Tumor Cell Lines
Published on: February 23, 2021
[Detection for therapeutic targets specifically expressed in myeloma side population cells]
Abstract:
ATP binding membrane transporter such as multi drug resistant protein (MDR1) and breast cancer resistance protein (BCRP) are highly activated in side population (SP) of various normal organs. It has been demonstrated that various primary as well as cancer cell lines also possess SP. Since SP cells have been also known as the cancer initiating cell rich population in various cancers, the population might play a crucial role in the pathogenesis of multiple myeloma. Recent our works demonstrated that G2/M (e.g. CCNB1, CDC2), centrosome (e.g.AURKB, CENP), polycomb (e.g. EPC1, EZH2) and proteasome (e.g. UBE3C, PSMA5) related genes were upregulated in the SP of myeloma cell lines and CD138-positive primary samples. Although myeloma has been known as incurable disease, discovery of new agents such as immunomodulatory drugs (lenalidomide) and proteasome inhibitor (bortezomib) provide improvement of prognosis of the tumor entity. These drugs might be effective to downregulate aforementioned aberrantly upregulated gene products in myeloma SP. Here we show some evidences of use of these drugs for targeting myeloma-SP cells.
Insights
Multiple myeloma side population (SP) cells, enriched in cancer-initiating cells, show upregulated genes involved in cell cycle and proteasome pathways. Targeting these SP cells with lenalidomide or bortezomib may offer new therapeutic strategies for multiple myeloma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cells
Context:
- Side population (SP) cells, characterized by ATP-binding membrane transporters like MDR1 and BCRP, are prevalent in various normal organs and cancer cell lines.
- SP cells are recognized as a reservoir of cancer-initiating cells, suggesting a significant role in the pathogenesis of multiple myeloma.
- Recent studies identified upregulated G2/M, centrosome, polycomb, and proteasome-related genes within the SP of myeloma cell lines and CD138-positive primary samples.
Purpose:
- To investigate the role of SP cells in multiple myeloma pathogenesis.
- To explore the potential of targeting upregulated genes in myeloma SP cells using existing therapeutic agents.
- To provide evidence for the efficacy of immunomodulatory drugs and proteasome inhibitors against myeloma-SP cells.
Summary:
- Multiple myeloma side population (SP) cells exhibit elevated expression of genes involved in cell cycle, centrosome function, polycomb repression, and proteasome activity.
- These SP cells are implicated as cancer-initiating cells in multiple myeloma.
- The study presents evidence suggesting that therapeutic agents like lenalidomide and bortezomib may effectively target and downregulate these aberrantly expressed genes in myeloma SP cells.
Impact:
- Highlights a potential therapeutic strategy for multiple myeloma by targeting cancer-initiating SP cells.
- Suggests that existing drugs may be repurposed to address the challenges posed by drug-resistant SP cells in multiple myeloma.
- Provides a foundation for further research into the specific mechanisms by which these drugs affect myeloma SP cells and their clinical implications.

