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Stingl, J. & Caldas, C. Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nature Rev. Cancer 7, 791-799

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Nature Reviews Cancer (Impact Factor: 29.54). 11/2007; 7(10):791-9. DOI: 10.1038/nrc2212
Source: PubMed

ABSTRACT 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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    • "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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    • "Of note, tumor cells with stem cell properties can develop from non-stem-like cells suggesting that stemness rather comprises a transitional functional phenotype than a continuous cell-specifi c feature and can be adjusted in critical situations such as environmental stress or nutrient changes (Gupta et al. 2011). It is believed that such cell-state dynamics in tumors are of particular signifi cance in tumorpathology and determine the aggressive nature of tumors, their tumor-seeding capacity and drug resistance (Stingl and Caldas 2007, Gupta et al. 2011). Due to their relative resistance to radiation and cytotoxic treatment cancer stem cells (CSC) may contribute to treatment failure and relapse (Creighton et al. 2009). "
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