Stingl J, Caldas CMolecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nat Rev Cancer 7: 791-799

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Nature Reviews Cancer (Impact Factor: 37.4). 11/2007; 7(10):791-9. DOI: 10.1038/nrc2212
Source: PubMed


Human breast cancers are heterogeneous, both in their pathology and in their molecular profiles. This suggests the hypothesis that breast cancers can initiate in different cell types, either breast epithelial stem cells or their progeny (transit amplifying cells or committed differentiated cells). In this respect, breast cancer could be viewed as being similar to haematological malignancies for which an analogous model has been proposed. Drawing such parallels might help to unravel the molecular nature of the initiating events in breast cancer and might have substantial clinical implications.

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Available from: John Stingl, Feb 10, 2015
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    • "There is mounting evidence suggesting that tumors are driven to grow by a small subfraction of cancer-inducing stem cells with the ability to initiate and maintain tumor growth and plasticity (Al-Hajj et al., 2003; O'Brien et al., 2007; Zhang et al., 2008; Hubbard and Gargett, 2010). Those studies led to investigations into tumor initiation and stemness, and subsequently to the hypothesis that certain tumors may arise from undifferentiated stem cells or that these undifferentiated stem cells undergo spontaneous dedifferentiation to give rise to cancer-inducing cells (Reya et al., 2001; Beachy et al., 2004; Lobo et al., 2007; Stingl and Caldas, 2007). Gene expression analysis has recently been utilized to identify the re-activation of pluripotency-related markers in different human tumors. "
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    Stem Cell Research 09/2014; 13(2). DOI:10.1016/j.scr.2014.08.001 · 3.69 Impact Factor
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    • "Cancer stem cells have the capacity of self-renewal, and are thought to be responsible for the generation of multiple cell lineages that are characteristic of many tumors [9]–[10]. Cancer stem cells have roles in tumorigenesis and resistance to therapy, so the identification of markers for cancer stem cell may provide important information regarding patient prognosis and response to therapy [11]–[12]. "
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    ABSTRACT: Stem cell markers are upregulated in various cancers and have potential as prognostic indicators. The objective of this study was to determine the expression of three stem cell markers, aldehyde dehydrogenase 1 (ALDH-1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), and Nanog, in esophageal squamous cell carcinoma (ESCC) tissues. Immunohistochemistry was used to measure the expression of ALDH-1, Bmi-1, and Nanog in ESCC tissues from 41 patients who received pre-operative chemoradiation. We evaluated the relationship between expression of these markers, and clinicopathological features, tumor regression grade (TRG), and 5-year overall survival (OS). There were no significant associations of ALDH-1 or Bmi-1 expression with age, gender, clinical stage, and treatments (p>0.05). However, patients with Nanog-positive tumors were significantly older than those whose tumors were Nanog-negative (p = 0.033). TRG after treatment was significantly associated with expression of ALDH-1 (p = 0.001), Bmi-1 (p = 0.004), and Nanog (p<0.001). Although OS was significantly better in patients with low TRGs (p = 0.001), there were no significant correlations between ALDH-1, Bmi-1, or Nanog with OS. Expression of ALDH-1, Bmi-1, and Nanog correlated with TRG, but not OS. Further large studies are necessary to fully elucidate the prognostic value of these stem cell markers for ESCC patients.
    PLoS ONE 08/2014; 9(8):e105676. DOI:10.1371/journal.pone.0105676 · 3.23 Impact Factor
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    • "One of the main biological challenges is heterogeneity of the CTC population. The significance of many molecularly different CTC subpopulations (i.e., cancer stem CTCs and CTCs with epithelial to mesenchymal transition [EMT]) has been clarified in the last decade [3,7,31,33,34], but quantitative and temporal heterogeneity of CTCs remains poorly understood. This, at least partly, can be explained by technical limitations of existing CTC assays that mainly use in vitro testing of blood samples. "
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