Open Access

ARTICLE

Epithelial-mesenchymal transition contributes to malignant phenotypes of circulating tumor cells derived from gastric cancer

Tiangen WU¹, Tianhao BAO^2,3, Daoming LIANG^1,*, Lin WANG^4,*

1 Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China
2 Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada
3 Mental Health Center of Kunming Medical University, Kunming, 650224, China
4 Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China

* Address correspondence to: Daoming Liang, ; Lin Wang,

BIOCELL 2019, 43(4), 293-298. https://doi.org/10.32604/biocell.2019.07841

Abstract

Circulating tumor cells (CTCs) are crucial to tumor metastasis, and they usually undergo epithelial– mesenchymal transition (EMT) in order to disseminate from the primary tumor. However, very little is currently known about the relationship between EMT and malignant phenotypes of CTCs in the context of gastric cancer. Therefore, this study aimed to investigate the contribution of EMT to malignant phenotypes of CTCs derived from gastric cancer cells. We xenografted MKN28 gastric cancer cells pretreated with transforming growth factor-beta 1 (TGFβ-1) into nude mice by intravenous injection. Next, we isolated CTCs from the blood of nude mice by gradient centrifugation and found that CTCs derived from MKN28 cells pretreated with TGFβ-1 had a significantly increased viability and invasion ability compared to MKN28 cells without TGFβ-1 treatment. Immunocytochemical staining showed lower expression of E-cadherin and higher expression of N-cadherin, vimentin, and β-catenin in CTCs derived from MKN28 cells pretreated with TGFβ-1. Furthermore, the expression of Wnt3a, β-catenin, cyclin D1, and c-Myc was significantly higher in CTCs derived from MKN28 cells pretreated with TGFβ-1. Taken together, these findings suggest that TGFβ promotes EMT and malignant phenotypes of gastric cancer cells. Furthermore, the malignant phenotypes of gastric cancer cells induced by TGFβ are maintained in CTCs derived from these cells. Targeting EMT in CTCs is a new approach to the treatment of gastric cancer relapse and metastasis.

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