Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 50, Issue 3, Pages 993-1001Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2017.3865
Keywords
fluid shear stress; metastasis; circulating tumor cell; epithelial to mesenchymal transition; epithelial cell adhesion molecule; cancer stem cell
Categories
Funding
- National Science Foundation (NSF) [1342388, 1604677]
- Research Experience for Undergraduates (REU) at the University of Alabama through NSF REU [1358750]
- Directorate For Engineering
- Div Of Civil, Mechanical, & Manufact Inn [1342388] Funding Source: National Science Foundation
- Directorate For Engineering
- Div Of Engineering Education and Centers [1358750] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1604677] Funding Source: National Science Foundation
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Metastasis is the leading cause of cancer deaths due to the spread of cancer cells through the blood vessels and the subsequent formation of secondary tumors. Metastasizing cancer cells in the human vasculature are called circulating tumor cells (CTCs) and are characterized to express the epithelial cell adhesion molecule (EpCAM). They are further known to survive physiological fluid shear stress (FSS) conditions. However, the effect of FSS on CTC molecular phenotype, such as the epithelial to mesenchymal transition (EMT) and cancer stem cell (CSC) expression, has not been extensively studied. Here, CTCs in FSS are evaluated in an in vitro model system. MCF7 and MDA-MB-231 breast cancer cell lines were grown in adherent and suspension culture media. The cell lines were tested for EMT and CSC genetic and protein markers using qRT-PCR and flow cytometry, respectively. Suspension cells showed a significantly increased EMT signature compared to adherent cells (p < 0.05), suggesting that they model cells detaching from primary tumors in vivo. Upon application of FSS, MCF7 and MDA-MB-231 cells did not show a significant change in EMT expression (p > 0.05), but there was a statistically significant increase of the CSC population in MCF7 suspension cultures (p < 0.05). These results with MCF7 suggest that CTCs can be modeled in vitro as non-adherent cancer cells in FSS and that they show an increased CSC-like signature during circulation, providing new insights to the importance of CSC-targeting strategies when treating metastatic patients.
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