Differential Expression of Cancer Stem Cell Markers ALDH1 and CD133 in Various Lung Cancer Subtypes

Roudi, Raheleh; Korourian, Alireza; Shariftabrizi, Ahmad; Madjd, Zahra

doi:10.3109/07357907.2015.1034869

Cited by 74 publications

(44 citation statements)

References 39 publications

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“…The latters display several stem cell-associated properties including self-renewal capability, higher clonogenic potential, resistance to chemotherapy and the expression of diverse CSCs markers, such as CD133, ALDH1 (detected as ALDH activity), Nanog and CD44. Noteworthy, none of analyzed markers showed a high and consistent expression in all the spheroids patient-derived LCSC lines, that were used in this study, thus confirming the heterogeneity in lung CSCs marker expression [46][47][48]. Our results show that CPTH6 preferentially inhibits cell viability and activates the apoptotic program of spheroid LCSCs with properties of CSCs.…”

Section: Discussionsupporting

confidence: 59%

Histone acetyltransferase inhibitor CPTH6 preferentially targets lung cancer stem-like cells

Martile¹,

Desideri²,

Luca³

et al. 2016

European Journal of Cancer

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Cancer stem cells (CSCs) play an important role in tumor initiation, progression, therapeutic failure and tumor relapse. In this study, we evaluated the efficacy of the thiazole derivative 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl] hydrazone (CPTH6), a novel pCAF and Gcn5 histone acetyltransferase inhibitor, as a small molecule that preferentially targets lung cancer stem-like cells (LCSCs) derived from non-small cell lung cancer (NSCLC) patients. Notably, although CPTH6 inhibits the growth of both LCSC and NSCLC cell lines, LCSCs exhibit greater growth inhibition than established NSCLC cells. Growth inhibitory effect of CPTH6 in LCSC lines is primarily due to apoptosis induction. Of note, differentiated progeny of LCSC lines is more resistant to CPTH6 in terms of loss of cell viability and reduction of protein acetylation, when compared to their undifferentiated counterparts. Interestingly, in LCSC lines CPTH6 treatment is also associated with a reduction of stemness markers. By using different HAT inhibitors we provide clear evidence that inhibition of HAT confers a strong preferential inhibitory effect on cell viability of undifferentiated LCSC lines when compared to their differentiated progeny. In vivo, CPTH6 is able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors, as evidenced by marked reduction of tumor-initiating capacity in limiting dilution assays. Strikingly, the ability of CPTH6 to inhibit tubulin acetylation is also confirmed in vivo. Overall, our studies propose histone acetyltransferase inhibition as an attractive target for cancer therapy of NSCLC.

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Section: Discussionsupporting

confidence: 59%

Histone acetyltransferase inhibitor CPTH6 preferentially targets lung cancer stem-like cells

Martile¹,

Desideri²,

Luca³

et al. 2016

European Journal of Cancer

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“…We therefore consider CD133 to be an appropriate CSC marker. Previous studies investigated the relationship between ALDH1A1 and CD133 (18,26,27). The results of these studies differed.…”

Section: Discussionmentioning

confidence: 40%

The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

Miyata

Oyama

Yoshimatsu

et al. 2017

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Abstract. Background/Aim: Aldehyde dehydrogenase-1A1 (ALDH1A1) and CD133 have been identified as markers of cancer stem cells (CSCsDespite continuous efforts to improve therapeutic response, lung cancer is the most common cause of cancer-related deaths in Japan, with adenocarcinoma by far the most common histology, accounting for nearly 70% of lung cancer cases (1). Cancer stem cells (CSCs) have the ability for selfrenewal and multipotently differentiate (2). CSCs may be highly resistant to chemotherapy and radiation, and be responsible for tumor initiation, progression and metastasis (3, 4). Accumulating evidence supports the existence of a CSC phenotype in human lung cancer (3, 5-7). The metabolic marker aldehyde dehydrogenase isoform 1A1 (ALDH1A1) and the cell-surface marker CD133 are reported to be markers of lung CSCs (3). We, therefore, investigated ALDH1A1 and CD133 expression in a retrospective cohort of 92 patients with lung adenocarcinoma. The objectives were to determine the association between ALDH1A1 and CD133 expression in lung adenocarcinoma, the relationship between their expression and the clinichopathological parameters, and the prognostic value of ALDH1A1 and CD133. Materials and MethodsPatient population and clinicopathological data. We examined a series of 154 Japanese patients with lung adenocarcinoma who underwent surgical treatment at Fukuoka-Wajiro Hospital, Fukuoka, Japan from 2006-2012. Ninety-two out of 154 (59.7%) patients were selected based on the following inclusion criteria: (i) no chemotherapy or radiotherapy before surgery, and (ii) the availability of an adequate paraffin block and clinicopathological data for the analysis. Follow-up information was obtained from the patients' records. Routinely collected clinicopathological data included age, gender, smoking history and pathological stage. There were 49 males (53%) and 43 females (47%), with a median age of 71 years (range=40-92 years) at the time of surgery; 43 (47%) patients were <70 years and 49 (53%) were ≥70 years of age. Half of the patients (n=46) had a smoking history. The pathological stages were: stage I, n=62 (67.4%); stage II, n=14 (15.2%); stage III, n=12 (13.0%); and stage IV, n=4 (4.4%) (TNM staging of lung cancer) (8). The median follow-up period was 1,702 days (range=4-3679 days). Recurrence was diagnosed by computed tomography alone or combined with positron-emission tomography.

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“…Although CD133 is expressed in various human tissues, its glycosylated epitopes specific for stem cells may be discordant or sometimes absent, making it difficult to identify this cell population (13). There may be transcriptional or post-translational modifications (14), leading to some degree of alteration in its expression, or variation in its expression in different tumors may be due to the use of antibodies from different clones (12). However, despite these limitations, recent results from different laboratories have shown significant association of CD133 (epitope-1) expression in a population of tumor cells with CSC characteristics in the brain, prostate, liver, and lung (15)(16)(17)(18).…”

mentioning

confidence: 99%

“…The CD133ϩve cells like CSC demonstrate significantly increased stemness, adhesion, motility, and expression of drug efflux gene (21-23) than CD133Ϫve tumor cells. Importantly, the presence of CD133ϩve tumor cells correlates well with poor prognosis, decreased survival, and increased lymph node metastasis in NSCLC patients (24 -26).Furthermore, in addition to CD133, aldehyde dehydrogenase 1 (ALDH1) is also used as a CSC marker in NSCLC (12,(27)(28)(29)(30) 4 The abbreviations used are: NSCLC, non-small cell lung carcinoma; CSC, cancer stem cell(s); D 2 DA, D 2 dopamine (DA) receptors; ERK1/2, extracellular signal-regulated kinases 1/2; MMP-9, matrix metalloproteinase-9; MTT, 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide; PI, propidium iodide. …”

mentioning

confidence: 99%

Activation of D2 Dopamine Receptors in CD133+ve Cancer Stem Cells in Non-small Cell Lung Carcinoma Inhibits Proliferation, Clonogenic Ability, and Invasiveness of These Cells

Roy

Nayak

et al. 2017

Journal of Biological Chemistry

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Edited by Xiao-Fan WangLung carcinoma is the leading cause of cancer-related death worldwide, and among this cancer, non-small cell lung carcinoma (NSCLC) comprises the majority of cases. Globally, lung cancers are considered to be the leading causes of cancer-related deaths, and non-small cell lung carcinoma (NSCLC) 4 is the predominant type of lung cancer, occurring in 85% of the cases (1, 2). The prognosis of NSCLC is poor, and the survival rate is only 15% after 5 years because many of these patients ultimately do not respond to chemotherapy and radiotherapy due to the presence of CSC (3-5). The CSC have the unique ability to promote tumor growth, recurrence, metastasis, and resistance to treatment (6, 7).Moreover, CD133, a surface glycoprotein with a five-transmembrane domain, has been widely used as a surface marker to identify CSC in many human tumors including NSCLC (8 -12). Although CD133 is expressed in various human tissues, its glycosylated epitopes specific for stem cells may be discordant or sometimes absent, making it difficult to identify this cell population (13). There may be transcriptional or post-translational modifications (14), leading to some degree of alteration in its expression, or variation in its expression in different tumors may be due to the use of antibodies from different clones (12). However, despite these limitations, recent results from different laboratories have shown significant association of CD133 (epitope-1) expression in a population of tumor cells with CSC characteristics in the brain, prostate, liver, and lung (15-18).There are now several reports that have further strengthened the concept of CD133ϩve tumor cells as CSC in NSCLC as these tumor cells possess the characteristics of CSC (18 -20). In contrast to the CD133Ϫve tumor cells, CD133ϩve tumor cells are more tumorigenic and resistant to radiation and anticancer drugs (18 -20). These cells also have a greater ability to form anchorage-independent floating spheres, proliferation, and tumor mass than the CD133Ϫve NSCLC cells. The CD133ϩve cells like CSC demonstrate significantly increased stemness, adhesion, motility, and expression of drug efflux gene (21-23) than CD133Ϫve tumor cells. Importantly, the presence of CD133ϩve tumor cells correlates well with poor prognosis, decreased survival, and increased lymph node metastasis in NSCLC patients (24 -26).Furthermore, in addition to CD133, aldehyde dehydrogenase 1 (ALDH1) is also used as a CSC marker in NSCLC (12,(27)(28)(29)(30) 4 The abbreviations used are: NSCLC, non-small cell lung carcinoma; CSC, cancer stem cell(s); D 2 DA, D 2 dopamine (DA) receptors; ERK1/2, extracellular signal-regulated kinases 1/2; MMP-9, matrix metalloproteinase-9; MTT, 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide; PI, propidium iodide.

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Differential Expression of Cancer Stem Cell Markers ALDH1 and CD133 in Various Lung Cancer Subtypes

Cited by 74 publications

References 39 publications

Histone acetyltransferase inhibitor CPTH6 preferentially targets lung cancer stem-like cells

Histone acetyltransferase inhibitor CPTH6 preferentially targets lung cancer stem-like cells

The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

Activation of D2 Dopamine Receptors in CD133+ve Cancer Stem Cells in Non-small Cell Lung Carcinoma Inhibits Proliferation, Clonogenic Ability, and Invasiveness of These Cells

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