Abstract
Circulating tumor cells (CTCs) are essential for the establishment of distant metastasis. Numerous studies have characterized CTCs as metastatic precursors; however, the molecular nature of CTCs has not been completely revealed yet due to the low number of CTCs in the blood stream. As an alternative approach, we developed a long-term suspension cell culture model using human breast cancer cell lines to mimic CTCs. We found that more than 40 passaged suspension cells acquired the ability to enhance metastasis like cancer stem cells. To identify molecular changes acquired during the suspension cell culture, we analyzed metabolic and lipidomic profiles as well as transcriptome in MDA-MB-468 suspension cells. Glutamate and leucine levels increased in suspension cells, and cholesterol synthesis pathway was altered. The inhibition of glutamate metabolic pathway decreased the proliferation of suspension cells compared to that of adherent cells. In the lipidomic profile, PC species containing long chain and polyunsaturated fatty acids increased in suspension cells and these species could be authentic and specific biomarkers for highly metastatic cancers. As this CTC-mimicking suspension cell culture model may easily apply to various types of cancer, we suggest this model as a great tool to develop therapeutic targets and drugs to eradicate metastatic cancer cells.
Highlights
Epithelial mesenchymal transition (EMT) is the first step for tumor cells to leave their original site
As this Circulating tumor cells (CTCs)-mimicking suspension cell culture model may apply to various types of cancer, we suggest this model as a great tool to develop therapeutic targets and drugs to eradicate metastatic cancer cells
Breast cancer can be classified into five subtypes based on gene expression profiling and immunohistochemical expression of estrogen receptor α (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2): luminal A, luminal B, HER2, and basal- and normal-like [19,20,21]
Summary
Epithelial mesenchymal transition (EMT) is the first step for tumor cells to leave their original site. As the dissemination of tumor cells mostly occurs through the blood stream after EMT, tumor cells that have been shed into the vasculature are known as circulating tumor cells (CTCs) [1]. CTCs have important prognostic and therapeutic implications and are useful for liquid biopsy, these cells are not detected because they exist in a very small amount. To overcome this hurdle, we cultured adherent tumor cells in suspension and continuously maintained in suspension to mimic CTCs or CSCs, and a comprehensive www.impactjournals.com/oncotarget and comparative analysis on gene expression and metabolism was performed to characterize suspension cells
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