E-cad-Fc-Matrix Enhances Cancer Stem-Like Properties and Induces Mesenchymal Features in Colon Cancer Cells.

Cancer stem cells (CSCs) are a subpopulation of tumor cells with properties of high tumorigenicity and drug resistance, which lead to recurrence and poor prognosis. Although a better understanding of CSCs is essential for developing cancer therapies, the scarcity of the CSC population has hindered such analyses. The aim of this study was to elucidate whether the E-cadherin-Fc chimera protein (E-cad-Fc) would enhance cancer stem-like properties because studies show that soluble E-cadherin stimulates the human epithelial growth factor receptors (EGFRs) and the downstream signaling pathways which are reported to play a crucial role in CSC. For this purpose we used ornithine decarboxylase (ODC)-degron-transduced (Degron(+)) KM12SM cells as a CSC model that retains relatively low CSC properties. Compared to cultures without E-cad-Fc treatment, we found that E-cad-Fc treatment further suppressed proteasome activity and largely enhanced cancer stem-like properties of ODC-degron-transduced KM12SM cells. These results include increased expression of stem cell markers Lgr5, Bmi-1, SOX9, CD44, and CD44v9, ALDH, and enhancement of robust spheroid formation, and chemoresistance to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP). These effects could be attributed to activation of EGFR pathway as identified by extensive phosphorylation of EGFR, ERK, PI3K, AKT, and mTOR. In SW480 cells, E-cad-Fc matrix induced some CSC markers such as CD44v9 and ALDH. We also found that E-cad-Fc matrix showed a high efficiency of inducing mesenchymal changes in the colon cancer cells. Our data suggest that the E-cad-Fc matrix may be an efficient material for enhancing CSC properties.