Quantitative Analyses of CD133 Expression Facilitate Researches on Tumor Stem Cells

Liao, Yongqiang; Hu, Xueqiang; Huang, Xuefeng; He, Chao

doi:10.1248/bpb.33.738

Cited by 20 publications

(16 citation statements)

References 23 publications

(27 reference statements)

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“…52 However, the hypothesis that AC133 recognizes a glycosylated epitope was questioned, 27 and and CD133 þ subpopulations in vitro as verified in western blot analyses were included in our study because a CD133 þ SW620 subfraction was also reported earlier to result in faster tumor formation and larger xenografts after subcutaneous or orthotopic injection into NOD/SCID or nude mice. 23,58 Our data, however, reveal, that CD133 À and CD133 þ SW620 subpopulations neither differ in clonogenic survival in vitro nor in tumor formation capacity in NMRI (nu/nu) mice. And, the CD133 À population of this cell line also appeared to rapidly re-express CD133 protein for presentation on the cell surface, a modulation particularly induced after in vivo engraftment.…”

Section: Discussionmentioning

confidence: 55%

Rapid re-expression of CD133 protein in colorectal cancer cell lines in vitro and in vivo

Peickert

Waurig

Dittfeld

et al. 2012

Laboratory Investigation

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Studies related to the cancer stem cell hypothesis are challenging because of the imperfect tools to identify cell populations of interest and controversy on the usefulness of established cancer cell lines. We previously found CD133 to not be selective for a tumor-propagating or radioresistant population in a near-diploid, microsatellite-instable colorectal carcinoma (CRC) cell line. Because of discrepant literature data, we herein systematically analyzed the behavior of microsatellite-stable cell line subpopulations reflecting the more frequent carcinogenesis pathway in spontaneous CRC. CD133 þ and CD133 À /low populations were isolated by fluorescence-activated cell sorting and further processed. HT29 and SW620 cells were studied in detail in monolayer and/or spheroid culture assays and upon subcutaneous injection in NMRI (nu/nu) mice using a limiting dilution approach. CD133À /low HT29 cells showed a significantly lower clonogenic survival and reduced spheroid formation capacity than their CD133 þ counterparts. However, the cell populations neither differed in growth kinetics and response to treatment in vitro nor in tumor formation capacity when injecting as low as 10 cells. CD133 À /low HT29 cells rapidly re-expressed CD133 protein in vitro and in vivo as shown by flow cytometry and/or western blot analyses, and they also showed a particular survival benefit under tissue normoxic conditions. In contrast, CD133 protein in the CD133 þ population was quite stable throughout culturing. The observation of CD133 re-expression and lack of difference in tumor take rate of subpopulations was confirmed in SW620 cells. Here, we found cell density to affect CD133 re-expression in the CD133À -sorted population. And even SW480 cells, classified as a CD133 À cell line, presented some CD133 protein on their surface upon in vivo engraftment. We conclude that (i) CD133 protein expression shows high plasticity in CRC cell lines, and (ii) in vitro CD133 status on the cell surface neither determines tumorigenic potential nor CD133 profile in vivo.

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Section: Discussionmentioning

confidence: 55%

Rapid re-expression of CD133 protein in colorectal cancer cell lines in vitro and in vivo

Peickert

Waurig

Dittfeld

et al. 2012

Laboratory Investigation

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“…These differences in previous reports could arise from using different antibodies, tissue samples (cell lines vs. human tissue), methods of detection (IHC expression vs. PCR based techniques) [34], and tissue sampling method (tissue microarray vs. individually mounted tissue slides) and method for scoring the positivity of CD133 IHC expression. To avoid the scoring bias and in view of a recent paper in which CD133 positivity was quantitatively graded [35], we used four-tiered scoring method comprising 0 (totally negative cases), 1+, 2+, and 3+ cases (CD133+ cells covering 1-10%, 11-50%, and 51-100%, of the tumor area, respectively). Nevertheless, we considered the 2+ and 3+ groups as CD133 positive.…”

Section: Discussionmentioning

confidence: 99%

CD133 expression is not an independent prognostic factor in stage II and III colorectal cancer but may predict the better outcome in patients with adjuvant therapy

et al. 2013

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BackgroundCancer stem cells (CSCs) are notorious for their capacity of tumor progression, metastasis or resistance to chemo-radiotherapy. However, the undisputed role of cancer stem marker, CD133, in colorectal cancers (CRCs) is not clear yet.MethodsWe assessed 271 surgically-resected stage II and III primary CRCs with (171) and without (100) adjuvant therapy after surgery. CD133 expression was analyzed by immunohistochemical (IHC) staining and real-time RT-PCR. CD133 promoter methylation was quantified by pyrosequencing.ResultsThe CD133 IHC expression was significantly correlated with mRNA expression (p=0.0257) and inversely correlated with the promoter methylation (p=0.0001). CD133 was expressed more frequently in rectal cancer (p=0.0035), and in moderately differentiated tumors (p=0.0378). In survival analysis, CD133 expression was not significantly correlated with overall survival (OS) (p=0.9689) as well as disease-free survival (DFS) (p=0.2103). However, CD133+ tumors were significantly associated with better OS in patients with adjuvant therapy compared to those without adjuvant therapy (p<0.0001, HR 0.125, 95% CI 0.052-0.299). But the patients with CD133- tumors did not show any significant difference of survival according to adjuvant therapy (p=0.055, HR 0.500, 95% CI 0.247-1.015).ConclusionsIn stage II and III CRCs, CD133 IHC expression may signify the benefit for adjuvant therapy although it is not an independent prognostic factor.

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“…It has been hypothesized that CSCs play a role in tumor chemoresistance. They have also been termed cancer initiating cells as they retain the ability to form colonies, and are also responsible for tumor recurrence and refractoriness (3)(4)(5)(6)(7)(8)(9). It has been suggested that colorectal cancer is caused by an alteration in the normal homeostasis of stem cells (Fig.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer

Padín-Iruegas¹,

Herranz-Carnero²,

Aguín-Losada³

et al. 2013

Oncology Reports

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Cancer stem cells play an important role in carcinogenesis and resistance to treatment and may lead to metastasis. The isolation of circulating stem cells involves cell sorting based on the presence of cell surface markers. Many surface markers such as CD133, c-Kit, SOX, OCT4 and TWIST have been reported. In the present study, we determined the expression of different stem cell markers and their variation in expression at different stages of the treatment process. Samples of EDTA blood were collected from metastatic colorectal cancer patients, and circulating cancer stem cells were isolated for the analysis of the expression of stem cell markers using RT-PCR. These findings were correlated with the response to therapy. All statistical analyses were performed using the GraphPad Prism 5.03 software. Significant differences were found in the expression levels of the markers CD133, SOX2, OCT4 and TWIST1. No differences were found in c-Kit expression. Correlation in the expression levels of most of the markers was observed. Expression of CD133, OCT4, SOX2 and TWIST1 had a predictive value for colon cancer behavior. Evaluation of this stem cell gene expression panel may be useful for predicting the response during the process of treatment, and the relative easy access to samples facilitates this method. Moreover the correlation between CD133 and TWIST1 expression may be associated with tumor regrowth and metastatic relapse.

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Quantitative Analyses of CD133 Expression Facilitate Researches on Tumor Stem Cells

Cited by 20 publications

References 23 publications

Rapid re-expression of CD133 protein in colorectal cancer cell lines in vitro and in vivo

Rapid re-expression of CD133 protein in colorectal cancer cell lines in vitro and in vivo

CD133 expression is not an independent prognostic factor in stage II and III colorectal cancer but may predict the better outcome in patients with adjuvant therapy

Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer

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