Chemoresistance‐Induced Epithelial‐Mesenchymal Transition of a Colorectal Cancer Cell Line

Abstract

Transdifferentiation of epithelial cells to mesenchymal cells is called epithelial‐mesenchymal transition (EMT). EMT is a normal process during embryogenesis, where epithelial cells lose their characteristics and become more motile mesenchymal cells. Invasive and metastatic characteristics of carcinoma cells in primary tumors are mediated by EMT. Specifically, the primary tumor loses cell‐cell adhesion normally mediated by E‐cadherin and attains mesenchymal markers such as vimentin. Also, transitioning cells attain increased intercellular separation and elongated shape with pseudopodia. Studies have shown that chemotherapy and radiation therapy lead to formation of resistant cells by transdifferentiation into EMT. To study chemoresistance‐induced EMT, colon cancer (DLD‐1) cells were treated with increasing concentrations of oxaliplatin (an anti‐cancer drug used to treat metastasized colon cancer) to develop a chemo‐resistant cell line (DLD‐1 OxR). These resistant cells show properties of EMT by morphologic and cell migration measures. Previously, we showed that curcumin, a phytochemical derived from turmeric, inhibited DLD‐1 proliferation: its effect on DLD‐1 OxR suggests inhibition as well. Future studies of DLD‐1 OxR will include characterization of mesenchymal marker expression.