Cancer stem cell markers are associated with adverse biomarker profiles and molecular subtypes of breast cancer

Tsang, Julia Y. S.; Huang, Yuhua; Luo, Min; Ni, Yun‐Bi; Chan, Siu‐Ki; Lui, Pauline Po Yee; Yu, Alex M C; Tan, Puay Hoon; Tse, Gary M.

doi:10.1007/s10549-012-2271-6

Cited by 67 publications

(59 citation statements)

References 33 publications

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“…The association with hormone unresponsiveness has been reported previously (Ginestier et al , 2007; Nalwoga et al , 2010; Zhou et al , 2010; Tsang et al , 2012). Although ER- and PR-negative tumours tend to be more aggressive, ALDH1 expression did not correlate with recurrence or death, and failed to predict survival, in our study.…”

Section: Discussionsupporting

confidence: 68%

ALDH1 expression is enriched in breast cancers arising in young women but does not predict outcome

2013

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Background:Tumours arising in younger women appear to be biologically more aggressive and tend to have a poorer outcome. Being relatively resistant to conventional treatments, breast cancer stem cells (CSCs) have been postulated as a possible cause of disease recurrence after treatment. In this study, we used ALDH1 as a CSC marker and determined whether ALDH1 expression correlated with clinical outcome in young women with breast cancer.Methods:The expression of ALDH1 was evaluated through immunohistochemistry on microarrayed cores obtained from 141 consecutive patients up to 35 years of age.Results:The expression of ALDH1 was observed in 25% (35 of 141) of tumours, in a median of 5% of cells. Younger women were 14 times more likely to have ALDH1-positive tumours (P<0.01, OR 14.4, 95% CI 4.34–48.09). The ALDH1 correlated independently with ER negativity (P=0.01, OR 0.33, 95% CI 0.15–0.77). There was no correlation with disease recurrence or breast cancer-related deaths.Conclusion:In younger women, ALDH1 was more highly expressed, and it correlated with ER negativity. It, however, did not predict survival in this study.

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Section: Discussionsupporting

confidence: 68%

ALDH1 expression is enriched in breast cancers arising in young women but does not predict outcome

2013

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“…They found that the combination of CD44 + /CD24 - and ALDEFLUOR activity enabled them to isolate tumor cells able to form tumors with fewer numbers compared to the cells sorted by ALDEFLUOR activity alone; however, they did not investigate the clinical implications of this combination 9 . Actually, recent studies have shown that a combined analysis of BCSC markers can robustly predict outcome, but it works only limited to a subset of breast cancer 48-50. The current study demonstrated that the combined BCSC phenotype with CD44 + /CD24 - and ALDH1A1 could be an independent predictor of PFS in TNBC.…”

Section: Discussionmentioning

confidence: 54%

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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“…Aggressive breast tumors have high MCSC content that promotes not only progression of the disease but also its recurrence and metastasis (49). As few as 500 stem cell/cancer stem cells, that express aldehyde dehydrogenase-1 (ALDH1) in aggressive human breast tumors, have been found to initiate xenograft formation in nude mice (50).…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Beige/Brown Adipose Markers from Host and Breast Cancer Cells Influence Xenograft Formation in Mice

Singh

Parveen

Basgen

et al. 2016

Molecular Cancer Research

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The initiation and progression of breast cancer is a complex process that is influenced by heterogeneous cell populations within the tumor microenvironment (TME). Although adipocytes have been shown to promote breast cancer development, adipocyte characteristics involved in this process remain poorly understood. In this study, we demonstrate enrichment of beige/brown adipose markers, contributed from the host as well as tumor cells, in the xenografts from breast cancer cell lines. In addition to uncoupling protein-1 (UCP1) that is exclusively expressed in beige/brown adipocytes, gene expression for classical brown (MYF5, EVA1 and OPLAH), as well as beige (CD137/TNFRSF9 and TBX1) adipocyte markers, were also elevated in the xenografts. Enrichment of beige/brown characteristics in the xenografts was independent of the site of implantation of the breast tumor cells. Early stages of xenografts showed an expansion of a subset of mammary cancer stem cells (MCSCs) that expressed PRDM16, a master regulator of brown adipocyte differentiation. Depletion of UCP1+ or Myf5+ cells significantly reduced tumor development. There was increased COX-2 (MT-CO2) expression, which is known to stimulate formation of beige adipocytes in early xenografts and treatment with a COX-2 inhibitor (SC236) reduced tumor growth. By contrast, treatment with factors that induce brown adipocyte differentiation in vitro led to larger tumors in vivo. A panel of xenografts derived from established breast tumor cells as well as patient-tumor tissues were generated that expressed key brown adipose tissue (BAT)-related markers and contained cells that morphologically resembled brown adipocytes. Implications This is the first report demonstrating that beige /brown adipocyte characteristics could play an important role in breast tumor development and suggest a potential target for therapeutic drug design.

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Cancer stem cell markers are associated with adverse biomarker profiles and molecular subtypes of breast cancer

Cited by 67 publications

References 33 publications

ALDH1 expression is enriched in breast cancers arising in young women but does not predict outcome

ALDH1 expression is enriched in breast cancers arising in young women but does not predict outcome

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

Increased Expression of Beige/Brown Adipose Markers from Host and Breast Cancer Cells Influence Xenograft Formation in Mice

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