Expression of ALDH1A1 and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis, tumor progression and cancer stem cell identification

Leinung, Martin; Ernst, Benjamin Philipp; Döring, Constanze; Wagenblast, Jens; Tahtali, Aykut; Diensthuber, Marc; Stöver, Timo; Geißler, Christin

doi:10.3892/ol.2015.3542

Cited by 30 publications

(27 citation statements)

References 36 publications

(30 reference statements)

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“…Westernblot analysis of representative NPC stem cell markers, ALDH1 and CD44 [ 20 ], revealed increased expression in PTEN−/CNE2 and PTEN−/CNE1 cells, relative to PTEN+ cells (Figure 1C ). As a functional measure of CSCs frequency [ 21 ], we tested the tumorsphere forming ability of PTEN−/+ CNE2 cells.…”

Section: Resultsmentioning

confidence: 99%

Radiation-resistant cancer stem-like cell properties are regulated by PTEN through the activity of nuclear β-catenin in nasopharyngeal carcinoma

Zhang¹,

Wang

Yao³

et al. 2017

Oncotarget

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Radiotherapy is the primary and most important treatment for nasopharyngeal carcinoma (NPC). Cancer stem-like cells (CSCs) have been shown to be resistant to radiation. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor gene has been suggested to play a role in stem cell self-renewal. In the present study, we sorted PTEN−/+ cells using a flow cytometer. The clone formation assay showed that PTEN− cells were more radioresistant than PTEN+ NPC cells. We found that PTEN− cells demonstrated a significant increase in tumorsphere formation and CSCs markers compared with PTEN+ cells. Silencing the expression of PTEN with siRNA resulted in increased expression of p-AKT, active β-catenin and Nanog. siPTEN cells irradiated showed more radioresistant and DNA damage than parental cells. We also confirmed that down-regulation of β-catenin expression with shRNA resulted in a reduced percentage of side population cells and expression of Nanog. shβ-catenin cells significantly decreased survivin expression at 4 Gy irradiation in PTEN− cells compared with PTEN+ cells. In siPTEN cells, β-catenin staining shifted from the cytoplasmic membrane to the nucleus. Furthermore, immunofluorescence showed that following irradiation of PTEN− cells, at 4 Gy, active β-catenin was mainly found in the nucleus. Immunohistochemistry analysis also demonstrated that the PTEN−/p-AKT+/β-catenin+/Nanog+ axis may indicate poor prognosis and radioresistance in clinical NPC specimens. Thus, our findings strongly suggest that PTEN− cells have CSCs properties that are resistant to radiation in NPC. PTEN exerts these effects through the downstream effector PI3K/AKT/β-catenin/Nanog axis which depends on nuclear β-catenin accumulation.

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Section: Resultsmentioning

confidence: 99%

Radiation-resistant cancer stem-like cell properties are regulated by PTEN through the activity of nuclear β-catenin in nasopharyngeal carcinoma

Zhang¹,

Wang

Yao³

et al. 2017

Oncotarget

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“…Our data showed that all markers but ALDH1A1 were increased in HT29-resistant cells. ALDH1A1 expression was undetected in HCT116 parental and drug-resistant cells, although, ALDH1A1 was proposed to characterize a subpopulation of cells with tumor-initiating or cancer stem cell properties in several malignancies (69,70). By contrast with HT29-resistant cells, only CD26 and CD166 showed some increase, but a very limited one, in HCT116/ DocR cells.…”

Section: Discussionmentioning

confidence: 99%

Acquisition of anticancer drug resistance is partially associated with cancer stemness in human colon cancer cells

Khoury

Corcos

Durand

et al. 2016

International Journal of Oncology

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Colorectal cancer (CRC) is one of the most aggressive cancers worldwide. Several anticancer agents are available to treat CRC, but eventually cancer relapse occurs. One major cause of chemotherapy failure is the emergence of drug-resistant tumor cells, suspected to originate from the stem cell compartment. The aim of this study was to ask whether drug resistance was associated with the acquisition of stem cell-like properties. We isolated drug-resistant derivatives of two human CRC cell lines, HT29 and HCT116, using two anticancer drugs with distinct modes of action, oxaliplatin and docetaxel. HT29 cells resistant to oxaliplatin and both HT29 and HCT116 cells resistant to docetaxel were characterized for their expression of genes potentially involved in drug resistance, cell growth and cell division, and by surveying stem cell-like phenotypic traits, including marker genes, the ability to repair cell-wound and to form colonospheres. Among the genes involved in platinum or taxane resistance (MDR1, ABCG2, MRP2 or ATP7B), MDR1 was uniquely overexpressed in all the resistant cells. An increase in the cyclin-dependent kinase inhibitor p21, in cyclin D1 and in CD26, CD166 cancer stem cell markers, was noted in the resistant cells, together with a higher ability to form larger and more abundant colonospheres. However, many phenotypic traits were selectively altered in either HT29- or in HCT116-resistant cells. Expression of EPHB2, ITGβ-1 or Myc was specifically increased in the HT29-resistant cells, whereas only HCT116-resistant cells efficiently repaired cell- wounds. Taken together, our results show that human CRC cells selected for their resistance to anticancer drugs displayed a few stem cell characteristics, a small fraction of which was shared between cell lines. The occurrence of marked phenotypic differences between HT29- and HCT116-drug resistant cells indicates that the acquired resistance depends mostly on the parental cell characteristics, rather than on the drug type used.

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“…In primary head and neck squamous cell carcinoma, the expression patterns of CD44 and EGFR were overlapping and were significantly connected ( 45 ). Although CD44 and EGFR have great impact on the initiation and progression of breast cancer, whether there was any connection between CD44 and EGFR still lacks direct evidence in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

CD44 correlates with clinicopathological characteristics and is upregulated by EGFR in breast cancer

Tian

et al. 2016

International Journal of Oncology

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Cluster of differentiation 44 (CD44), a well-known transmembrane glycoprotein, serves as a promoting factor in the carcinogenesis and progression of a variety of neoplasms. Previous studies have demonstrated that aberrant expression of CD44 was associated with the initiation, invasion, metastasis, and therapy-resistance of breast cancer, but whether there was any association between CD44 and pathological characteristics of breast cancer or epidermal growth factor receptor (EGFR) has not been clearly elucidated. In this study, we utilized public microarray data analysis and tissue microarray technologies to display that CD44 level was enhanced in breast cancer and was significantly correlated with histological grade and the status of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 (HER2) and EGFR. Furthermore, mRNA expression of CD44 in breast tumors was positively correlated with basal cytokeratin markers KRT5 and KRT17, but inversely associated with luminal marker FOXA1. Besides, Kaplan-Meier analysis showed that high CD44 mRNA level had adverse impact on the progression-free survival of patients with HER2-expressing or basal-like breast cancer. Functionally, inhibition of EGFR activity by erlotinib impaired the invasion and migration ability of breast cancer cell lines. Western blot assays demonstrated that erlotinib treatment decreased the expression of CD44, accompanied with the reduced protein levels of mesenchymal and cancer stem cell markers. Collectively, this study suggested that the expression of CD44 was upregulated by EGFR pathway and CD44 had a robust impact on the development of breast cancer.

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Expression of ALDH1A1 and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis, tumor progression and cancer stem cell identification

Cited by 30 publications

References 36 publications

Radiation-resistant cancer stem-like cell properties are regulated by PTEN through the activity of nuclear β-catenin in nasopharyngeal carcinoma

Radiation-resistant cancer stem-like cell properties are regulated by PTEN through the activity of nuclear β-catenin in nasopharyngeal carcinoma

Acquisition of anticancer drug resistance is partially associated with cancer stemness in human colon cancer cells

CD44 correlates with clinicopathological characteristics and is upregulated by EGFR in breast cancer

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