Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer.

Abstract

Esophageal cancer is one of the most lethal solid malignancies. Mounting evidence demonstrates that cancer stem cells (CSCs) are able to cause tumor initiation, metastasis and responsible for chemotherapy and radiotherapy failures. As CSCs are thought to be the main reason of therapeutic failure, these cells must be effectively targeted to elicit long-lasting therapeutic responses. We aimed to enrich and identify the esophageal cancer cell subpopulation with stem-like properties and help to develop new target therapy strategies for CSCs. Here, we found esophageal cancer cells KYSE70 and TE1 could form spheres in ultra low attachment surface culture and be serially passaged. Sphere-forming cells could redifferentiate and acquire morphology comparable to parental cells, when return to adherent culture. The sphere-forming cells possessed the key criteria that define CSCs: persistent self-renewal, overexpression of stemness genes (SOX2, ALDH1A1 and KLF4), reduced expression of differentiation marker CK4, chemoresistance, strong invasion and enhanced tumorigenic potential. SB525334, transforming growth factor-beta 1(TGF-β1) inhibitor, significantly inhibited migration and invasion of sphere-forming stem-like cells and had no effect on sphere-forming ability. In conclusion, esophageal cancer sphere-forming cells from KYSE70 and TE1 cultured in ultra low attachment surface possess cancer stem cell properties, providing a model for CSCs targeted therapy. TGF-β1 promotes the migration and invasion of sphere-forming stem-like cells, which may guide future studies on therapeutic strategies targeting these cells.

• Authors: Dongli Yue, Zhen Zhang, Jieyao Li, Xinfeng Chen, Yu Ping, Shasha Liu, Xiaojuan Shi, Lifeng Li, Liping Wang, Lan Huang, Bin Zhang, Yan Sun, Yi Zhang
• Journal: Experimental cell research (Exp Cell Res) Vol. 336 Issue 1 Pg. 141-9 (Aug 01 2015) ISSN: 1090-2422 [Electronic] United States
• PMID: 26096658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• KLF4 protein, human
• Klf4 protein, mouse
• Kruppel-Like Factor 4
• RNA, Messenger
• Transforming Growth Factor beta1

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Cell Differentiation (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Drug Resistance, Neoplasm
• Esophageal Neoplasms (drug therapy, metabolism, pathology)
• Female
• Humans
• Kruppel-Like Factor 4
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Spheroids, Cellular (drug effects, metabolism, pathology)
• Transforming Growth Factor beta1 (pharmacology)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays