title: Fluid shear stress induces cancer stem cell-like phenotype in MCF7 breast cancer cell line without inducing epithelial to mesenchymal transition.
abstract: 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.
authors.affiliation: Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, USA.
authors.forename: Ursula L
authors.initials: UL
authors.lastname: Triantafillu
authors.affiliation: Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, USA.
authors.forename: Seungjo
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Chemical Engineering, Kansas State University, Manhattan, KS, USA.
authors.forename: Nikki L
authors.initials: NL
authors.lastname: Klaassen
authors.affiliation: Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Raddatz
authors.affiliation: Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, USA.
authors.forename: Yonghyun
authors.initials: Y
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D057446:Hydrodynamics; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D013312:Stress, Physiological
chemical_list: D014408:Biomarkers, Tumor