Epithelial-Mesenchymal Transition Associates with Maintenance of Stemness in Spheroid-Derived Stem-Like Colon Cancer Cells

Abstract

Despite earlier studies demonstrating characteristics of colon cancer stem cells (CCSCs) and the role of epithelial-mesenchymal transition (EMT) in tumor development, it remains controversial as to the relationship between CCSCs and EMT. In this study, in order to present an insight into this relationship in colon cancer, we developed HCT116 and HT29 sphere models, which are known to be the cells enriching cancer stem cells. Compared to their parental counterparts, spheroid cells displayed lower homotypic/heterotypic adhesion but higher in vitro migratory/invasive capacity, as well as higher tumorigenic and metastatic potential in vivo. The spheroid cells also demonstrated down-regulated E-cadherin and up-regulated α-SMA and Vimentin expression, which is the typical phenotype of EMT. In order to explore whether this phenomenon is associated to activation of Wnt/β-catenin pathway, we detected several key signaling molecules. Compared with their parental cells, HCT116 and HT29 spheroid cells demonstrated down-regulated expression of GSK3β, but up-regulated expression of Slug and Snail. And also, the up-regulation of nucleus β-catenin in spheroid cells indicated that the free β-catenin transferred from cytoplasm to cell nucleus. Our findings indicate that spheroid cells have the characteristics of colon cancer stem cells, and EMT may account for their stemness and malignancy. And persistent activation of Wnt/β-catenin pathway may play an important role in the EMT of CCSCs.

New ex-ovo colorectal-cancer models from different SdFFF-sorted tumor-initiating cells

“…3Bd), HCT116 tumors did not express CK20 (Fig. 3Ad), a differentiated epithelial cell marker in CRC [29,30]. In agreement with this data, our previous study revealed that HCT116 cells were CK20 negative and WiDr cells were CK20 positive in vitro [25], and these properties were maintained after Matrigel culture and graft on the CAM.…”

β-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma

“…Vimentin expression was speculatively correlated with the progression of NPC, which was supported by an investigation in 122 NPC patients showing that high nuclear vimentin expression was correlated significantly with advanced clinical stage [33]. Up-regulated vimentin and downregulated E-cadherin are the typical phenotypes of epithelial-mesenchymal transition (EMT) which contributes to tumor invasion and metastasis [34]. Involvement of E-cadherin, vimentin, EpCAM, and β-catenin in cell adhesion and migration implied an intricate mechanism in tumor invasion and metastasis.…”

TGFβ signaling regulates epithelial–mesenchymal plasticity in ovarian cancer ascites-derived spheroids

“…On that note, E-cadherin is less immediately responsive particularly upon reattachment, perhaps indicating a delay to complete MET thereby facilitating spheroid cell motility and invasion. Induction of an EMT phenotype has been observed in other spheroid systems, usually in concert with stem-like cells (Mani et al 2008, Han et al 2013; however, these reports have not described whether or not the EMT phenotype is reversible. It may be that this plasticity is a particularly unique characteristic of metastatic ovarian cancer, not unlike its almost exclusive mode of intraperitoneal spread which is unique when compared among other carcinomas.…”