Comparative proteomics of glioma stem cells and differentiated tumor cells identifies S100A9 as a potential therapeutic target
Song Chen1, Hongxin Zhao, Jinmu Deng
1Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Abstract:
Recent studies have suggested the existence of a small subset of cancer cells called cancer stem cells (CSCs), which possess the ability to initiate malignancies, promote tumor formation, drive metastasis, and evade conventional chemotherapies. Elucidation of the specific signaling pathway and mechanism underlying the action of CSCs might improve the efficacy of cancer treatments. In this study, we analyzed differentially expressed proteins between glioma stem cells and differentiated tumor cells isolated from the human glioma cell line, U251, via iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis to identify proteins correlated with specific features of CSCs. Out of a total data set of 559 identified proteins, 29 proteins were up-regulated in the glioma stem cells when compared with the differentiated cells. Interestingly, The expression level of S100A9 was fivefold higher in glioma stem cells than differentiated cells. Similar results were also observed in glioma stem cells derived from other glioma cells. More importantly, knockdown of S100A9 by RNA interference suppressed the proliferation of glioma stem cell line and decreased the growth of xenograft tumors in vivo. Taken together, these results indicate that the tumorigenesis potential of CSCs arises from highly expressed S100A9.
Insights
Cancer stem cells (CSCs) drive tumor growth and metastasis. This study found that high S100A9 expression in glioma stem cells fuels their tumorigenic potential, suggesting S100A9 as a therapeutic target.
Area of Science:
- Oncology
- Cancer Stem Cell Biology
- Proteomics
Background:
- Cancer stem cells (CSCs) are implicated in tumor initiation, metastasis, and therapy resistance.
- Understanding CSC mechanisms is crucial for improving cancer treatment efficacy.
Purpose of the Study:
- To identify proteins associated with cancer stem cell features.
- To investigate the role of differentially expressed proteins in glioma stem cell tumorigenesis.
Main Methods:
- Proteomic analysis using iTRAQ-tagging and 2D LC-MS/MS.
- Comparison of protein expression between glioma stem cells and differentiated tumor cells (U251 cell line).
- RNA interference to assess the functional role of S100A9.
Main Results:
- Identified 559 proteins, with 29 upregulated in glioma stem cells.
- S100A9 expression was fivefold higher in glioma stem cells compared to differentiated cells.
- S100A9 knockdown inhibited glioma stem cell proliferation and reduced xenograft tumor growth in vivo.
Conclusions:
- Highly expressed S100A9 is linked to the tumorigenic potential of cancer stem cells.
- S100A9 plays a critical role in glioma stem cell proliferation and tumor growth.
- Targeting S100A9 may offer a novel therapeutic strategy for glioma.
