Strong correlation between N-cadherin and CD133 in breast cancer: role of both markers in metastatic events

Bock, Carolin; Kühn, Christina; Ditsch, Nina; Krebold, R; Heublein, Sabine; Mayr, Doris; Doisneau-Sixou, Sophie F.; Jeschke, Udo

doi:10.1007/s00432-014-1750-z

Cited by 35 publications

(36 citation statements)

References 40 publications

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“…It has been reported that CD133 expression correlates significantly with TNBC subtype 30, 47. However, the biologic function of CD133 in TNBC has not yet been well established and its prognostic role still remains debated 24, 25. We did not find any evidence of CD133 in predicting aggressive properties and poor outcome in TNBC.…”

Section: Discussioncontrasting

confidence: 73%

“…Studies in vitro have proven that CD133 is suitable for enriching BCSCs in TNBC 22, 23. For CD133+ phenotype, some studies documented poor prognosis in TNBC 24, while others did not 25. As the expression of these BCSC markers varied among different breast cancer subtypes, it appeared that each BCSC marker could have distinct clinical significance in different subgroups of breast cancers.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

Yang¹,

Cao²,

Sun³

et al. 2016

Int. J. Biol. Sci.

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Triple-negative breast cancer (TNBC) is a tumor subtype with aggressive behavior and poor clinical outcome for lacking effective therapies. Breast cancer stem cells (BCSCs) have been suggested to have tumor-initiating properties, but it remains unclear whether their presence contributes to the increased aggressiveness and poor prognosis of TNBC. Also, the breast cancers display frequent inter- and intra-tumor heterogeneity, which adds the complexity in diagnosis and predicting prognosis. Here we investigated the clinical relevance and prognostic value of the BCSC markers, CD44+/CD24-, aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and CD133 in 88 TNBC cases. We found that a few patients displayed spatial heterogeneity of the BCSC markers in expression, which was defined as intratumor stemness heterogeneity (ITSH) below. There was no significant correlation between any BCSC marker alone or ITSH and progression-free survival (PFS). Interestingly, the combined BCSC phenotype by CD44+/CD24- and ALDH1A1 was significantly associated with worse PFS (P = 0.009). Further stratification analysis revealed that this combined BCSC phenotype was an independent prognostic factor for PFS in some subgroups. In conclusion, we demonstrated the existence of ITSH in TNBC and found that the ITSH as well as a single BCSC marker was not significantly associated with survival, whereas combing the analysis of BCSC markers could improve prognostic value. Our findings may lead to an improvement of prognostic indicators in TNBC.

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Section: Discussioncontrasting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

Yang¹,

Cao²,

Sun³

et al. 2016

Int. J. Biol. Sci.

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“…Many cancer stem cell markers have been identified including CD133, CD44 + /CD22 − , and ALDH1 + in which CD133 is widely used as a cell surface marker in many cancer types including breast cancer . However, many groups commonly use ALDH1 in BCa, and this study confirms that high ALDH1 expression correlates with disease progression .…”

Section: Discussionsupporting

confidence: 72%

Targeting aberrant expression of Notch‐1 in ALDH⁺ cancer stem cells in breast cancer

Pal

Kolluru

Chandrasekaran

et al. 2016

Molecular Carcinogenesis

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We have previously reported that high aldehyde dehydrogenase (ALDH) enzyme activity in breast cancer cells results in breast cancer stem cell (BCSC) properties by upregualting Notch-1 and epithelial mesenchymal markers. This results in chemoresistance in breast cancer. Here, we examined the functional and clinical significance of ALDH expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues (Grade- II and III) versus normal breast tissues. Injection of BCSC (ALDH and CD44 /CD22 ) cells resulted in aggressive tumor growth in athymic mice versus ALDH cells. The ALDH and CD44 /CD22 tumors grow rapidly and are larger than ALDH tumors which were slow growing and smaller. Molecularly, ALDH tumors expressed higher expression of Notch-1 and EMT markers than ALDH tumors. Oral administration of the naturally occurring Psoralidin (Pso, 25 mg/kg of body weight) significantly inhibited the growth in ALDH and ALDH tumors as well. Psoralidin inhibited Notch-1 mediated EMT activation in ALDH and ALDH tumors-this confirms our in vitro findings. Our results suggest that Notch-1 could be an attractive target and inhibition of Notch-1 by Psoralidin may prevent pathogenesis of breast cancer as well as metastasis. © 2016 Wiley Periodicals, Inc.

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“…The high level of CDH-associated SC-TFs such as FOXM1, MCM2, SOX9, and SNAI1 were concurrent with the overexpression of CDH2, 4, 6, and 17 (Table 1), but mutually exclusive with the decrease of CDH1 (Supplementary Table S2), strongly suggested that the enrichment of CSCs was more closely related to the high of CDH2, 4, 6, and 17, but not to the low of CDH1. Consistently, CDH2 has been identified as an indicator of EMT, and strongly correlated with CD133, one of the stem cell markers [11, 12, 83]. Moreover, CDH2 has a role in cell migration and metastasis over CDH1.…”

Section: Discussionmentioning

confidence: 79%

Cadherins Associate with Distinct Stem Cell-Related Transcription Factors to Coordinate the Maintenance of Stemness in Triple-Negative Breast Cancer

Yang

Zhao

Cui

et al. 2017

Stem Cells International

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Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with poor prognosis and is enriched in cancer stem cells (CSCs). However, it is not completely understood how the CSCs were maintained in TNBC. In this study, by analyzing The Cancer Genome Atlas (TCGA) provisional datasets and several small-size breast datasets, we found that cadherins (CDHs) 2, 4, 6, and 17 were frequently amplified/overexpressed in 47% of TNBC while E-cadherin (CDH1) was downregulated/mutated at 10%. The alterations of CDH2/4/6/17 were strongly associated with the elevated levels of several stem cell-related transcription factors (SC-TFs) including FOXM1, MCM2, WWTR1, SNAI1, and SOX9. CDH2/4/6/17-enriched genes including FOXM1 and MCM2 were also clustered and regulated by NFY (nuclear transcription factor Y) and/or EVI1/MECOM. Meanwhile, these SC-TFs including NFYA were upregulated in TNBC cells, but they were downregulated in luminal type of cells. Furthermore, small compounds might be predicted via the Connectivity Map analysis to target TNBC with the alterations of CDH2/4/6/17 and SC-TFs. Together with the important role of these SC-TFs in the stem cell regulation, our data provide novel insights into the maintenance of CSCs in TNBC and the discovery of these SC-TFs associated with the alterations of CDH2/4/6/17 has an implication in targeted therapy of TNBC.

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Strong correlation between N-cadherin and CD133 in breast cancer: role of both markers in metastatic events

Abstract: N-cadherin and CD133 expressions are strongly correlated and N-cadherin appears as a potential metastases marker in a specific patient subpopulation.

Cited by 35 publications

References 40 publications

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

Targeting aberrant expression of Notch‐1 in ALDH⁺ cancer stem cells in breast cancer

Cadherins Associate with Distinct Stem Cell-Related Transcription Factors to Coordinate the Maintenance of Stemness in Triple-Negative Breast Cancer

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Strong correlation between N-cadherin and CD133 in breast cancer: role of both markers in metastatic events

Abstract: N-cadherin and CD133 expressions are strongly correlated and N-cadherin appears as a potential metastases marker in a specific patient subpopulation.

Cited by 35 publications

References 40 publications

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

Targeting aberrant expression of Notch‐1 in ALDH+ cancer stem cells in breast cancer

Cadherins Associate with Distinct Stem Cell-Related Transcription Factors to Coordinate the Maintenance of Stemness in Triple-Negative Breast Cancer

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Targeting aberrant expression of Notch‐1 in ALDH⁺ cancer stem cells in breast cancer