ICAM1 Is a Potential Cancer Stem Cell Marker of Esophageal Squamous Cell Carcinoma

• Published in: PloS one 2015-11, Vol.10 (11), p.e0142834-e0142834
• Main Authors: Tsai, Sheng-Ta, Wang, Po-Jen, Liou, Nia-Jhen, Lin, Pei-Shan, Chen, Chung-Hsuan, Chang, Wei-Chao
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Biochemistry; Biomarkers, Tumor - metabolism; Cancer; Cancer therapies; Carcinogenesis - metabolism; Carcinogenesis - pathology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Care and treatment; CD44 antigen; Cell adhesion; Cell Line, Tumor; Cell migration; Chemotherapy; Cytotoxicity; Deoxyribonucleic acid; Development and progression; DNA; DNMT1 protein; Drug resistance; Drug Resistance, Neoplasm; Esophageal cancer; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma; Esophagus; Gene Knockdown Techniques; Genetic aspects; Genomics; Health aspects; Hospitals; Humans; Hyaluronan Receptors - metabolism; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - metabolism; Liver cancer; Medical diagnosis; Medical prognosis; Membrane proteins; Membrane Proteins - metabolism; Mesenchyme; Metastasis; Mice, Inbred NOD; Mice, SCID; Molecular biology; Neoplasm Metastasis; Neoplastic Stem Cells - metabolism; p53 Protein; Patient outcomes; Polymerase chain reaction; Protein expression; Proteins; Proteomics; R&D; Radiation; Reproducibility of Results; Research & development; Risk factors; Signal Transduction; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Squamous cell carcinoma; Stem cells; Systematic review; Tumor cell lines; Tumor proteins; Tumor Suppressor Protein p53 - metabolism; Tumorigenesis; Tumors; Xenografts; Xenotransplantation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0142834

Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC) is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1) was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC.