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

ABSTRACT: 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.

SUBMITTER: Tsai ST

PROVIDER: S-EPMC4646358 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Tsai Sheng-Ta ST Wang Po-Jen PJ Liou Nia-Jhen NJ Lin Pei-Shan PS Chen Chung-Hsuan CH Chang Wei-Chao WC

PloS one 20151116 11

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 ...[more]

PMID: 26571024

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Project description:Esophageal squamous cell carcinoma (ESCC) is highly malignant with highly invasive and metastatic capabilities and poor prognosis. It is believed that the ESCC cancer stem-like cells (ECSLCs) are critical for tumorigenicity, invasion and metastasis of ESCC. However, the properties of ECSLCs vary with different markers used in isolation, so that new and more effective markers of ECSLCs need to be identified. This study aimed to estimate the potentiality of Cripto-1 (CR-1) as an ECSLC surface marker and investigate the clinical significance of CR-1 expression in ESCC.ESCC cells with CR-1 high or CR-1low were obtained by flow cytometry then their self-renewal capability and tumorigenicity were compared by colony and limiting dilution sphere formation analysis in vitro and xenograft in nude mice in vivo, respectively. Knockdown of CR-1 expression in ESCC cells was conducted with short hairpin RNA. Cell migration and invasion were examined by scratch test and matrigel transwell assay, respectively. Metastatic capability of ESCC cells was assayed by a mouse tail vein metastasis model. The levels of CR-1 expression in cancerous and paired adjacent normal tissues were assessed by IHC and qRT-RCR.CR-1high subpopulation of ESCC cells isolated by FACS expressed high level of genes related to stemness and epithelial-mesenchymal transition (EMT), and possessed high capacities of self-renewal, tumorigenesis, invasion and metastasis. Suppression of CR-1 expression significantly reduced the expression of stemness- and EMT-related genes and the capabilities of self-renewal in vitro, tumorigenicity and metastasis in vivo in ESCC cells. In the clinical ESCC specimens, the expression levels of CR-1 in cancerous tissues were positively correlated to TNM stage, invasive depth, and lymph node metastasis. Cox regression analysis indicated that CR-1 was an independent indicator of prognosis. The expression of CR-1 was found overlapping with aldehyde dehydrogenase 1A1 (ALDH1A1), an intracellular marker for ESCLCs, in ESCC cell lines and specimens.CR-1 is a functional and cell surface ECSLC marker, and an independent prognostic indicator as well as a potential therapeutic target for ESCC.

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

Publications

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

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