Detection and analysis of mammary gland stem cells

Stingl, John

doi:10.1002/path.2457

Cited by 140 publications

(168 citation statements)

References 95 publications

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“…CD14 is a surface protein, which is expressed in monocytes/macrophages (41,42), being often used, in the literature, as a stem cell marker (11). This protein is one of the useful markers used to identify mouse mammary progenitor cells (43). Our results show that the proportion of CD14 1 cells is higher than 60% in the nontumorigenic MCF10-A cell line and less than 15% in the Hs578-T tumorigenic and metastatic cell line.…”

Section: Discussionmentioning

confidence: 70%

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

et al. 2012

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The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis on the basis for tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized and relatively rare cell population, which is responsible for tumor initiation, self-renewal, and maintenance, in addition to accumulation of mutation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different genetic markers have been used to isolate breast CSCs, none of which have been correlated with the tumorigenicity or metastatic potential of the cells, limiting their precise characterization and clinical application in the development of therapeutic protocols. Here, we sought for subpopulations of CSCs by analyzing 10 judiciously chosen stem cell markers in a normal breast cell line (MCF10-A) and in four human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and Hs578-T) displaying different degrees of metastatic and invasiveness potential. We were able to identify two markers, which are differentially expressed in nontumorigenic versus tumor cells. The CD90 marker was highly expressed in the malignant cell lines. Interestingly, the CD14 molecule displayed higher expression levels in the nontumorigenic cell line. Therefore, we demonstrated that these two markers, which are more commonly used to isolate and characterize stem cells, are differentially expressed in breast tumor cells, when compared with nontumorigenic breast cells. ' 2012 International Society for Advancement of Cytometry Key terms CD90; Thy-1; breast cancer; cancer stem cell; CD14; breast cancer stem cell

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Section: Discussionmentioning

confidence: 70%

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

et al. 2012

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“…Apart from the existence of genetically distinctive non-modal populations, intra-tumour phenotypic diversity can be explained by non-genetic mechanisms, including epigenetic regulation of genes Intra-tumour genetic heterogeneity in breast cancer 563 and molecular networks, epithelial-to-mesenchymal transition, interaction with specific niches and tumour microenvironment [2,[7][8][9][10][11], and by the 'cancer stem cell' hypothesis [12][13][14][15][16]. This hypothesis proposes that the intra-tumour heterogeneity stems from, and is maintained by, a small population of cells (the socalled 'cancer stem cells'), which give rise to more differentiated cells and thus create the phenotypic diversity of tumours [2,12,15,16].…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas

Geyer

Weigelt

Natrajan

et al. 2010

The Journal of Pathology

187

159

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Cancers may be composed of multiple populations of submodal clones sharing the same initiating genetic lesions, followed by the acquisition of divergent genetic hits. Intra-tumour genetic heterogeneity has profound implications for cancer clinical management. To determine the extent of intra-tumour genetic heterogeneity in breast cancers, and whether the morphological diversity of breast cancers is underpinned by divergent genetic aberrations, we analysed the genomic profiles of microdissected, morphologically distinct components of six metaplastic breast carcinomas, tumours characterized by the presence of morphological areas with divergent differentiation. Each morphologically distinct component was separately microdissected and subjected to high-resolution microarray-based comparative genomic hybridization. Each component was also analysed by immunohistochemistry and in situ hybridization. Clonal relationship between the distinct components was tested by TP53 sequencing and human androgen receptor (HUMARA) X-chromosome inactivation assay. In the majority of cases, all morphologically distinct components from each case were clonal and displayed remarkably similar genetic profiles. In two cases, however, morphologically distinct components harboured specific genetic aberrations. In an adenosquamous carcinoma, the differences were such that only 20% of the genome harboured similar copy number changes. The squamous component displayed EGFR gene amplification, EGFR over-expression and lack of expression of hormone receptors, whereas the lobular component displayed the reverse pattern. The components of a biphasic spindle cell carcinoma harboured similar gains, losses, amplifications of 9p23 and 17q12 (HER2 ) and identical TP53 mutations, suggesting that these were relatively early events in the development of this tumour; however, each component displayed divergent focal amplifications. Importantly, the metastatic deposit of this case, despite harbouring a TP53 mutation identical to that found in the primary tumour, harboured additional specific focal amplifications. This proof-of-principle study provides direct evidence of intra-tumour genetic heterogeneity in breast cancers, and shows that in some cases morphological diversity may be underpinned by distinct genetic aberrations.

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“…The molecular and cellular processes in mammospheres are similar as those in developing alveoli of the mammary gland [20]. Hierarchically, mammary cells range from terminally differentiated cells to undifferentiated progenitors and stem cells, the latter two being likely targets for malignant transformations in cancer [21]. It was shown that an entire mammary gland can be reconstituted from a single mammary stem cell [22].…”

Section: D Organization-mammosphere Formationmentioning

confidence: 90%

Development of an In Vitro Goat Mammary Gland Model: Establishment, Characterization, and Applications of Primary Goat Mammary Cell Cultures

Ogorevc¹,

Zorc²,

Dovč³

2018

Goat Science

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Alternatives to animal experiments, based on in vitro methodologies, have been suggested and adopted in the last decades in order to completely substitute or to reduce animal numbers in in vivo assays. In this chapter we describe methods for establishment, maintenance, and characterization of primary goat mammary epithelial cell cultures (pgMECs) and possible applications for which the derived primary cell model can be used instead of in vivo experiments. The established cell lines were grown in vitro for several passages and remained hormone and immune responsive and capable of milk protein synthesis. Knowledge on goat mammary cells and their manipulation is applicable to different fields of research; for example, it could be used in basic research to study mammary development and lactation biology, in agriculture to enhance lactation yield and persistency or to produce milk with special characteristics, in biopharma to express recombinant proteins in goat milk, or in biomedicine to study lactation, mammary development, and pathology, including neoplasia. The established cells represent an adequate surrogate for mammary gland; were successfully used to study mammary gland immunity, lactation, and mammary stem/progenitor cells; and have a potential to be used for other purposes.

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Detection and analysis of mammary gland stem cells

Cited by 140 publications

References 95 publications

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas

Development of an In Vitro Goat Mammary Gland Model: Establishment, Characterization, and Applications of Primary Goat Mammary Cell Cultures

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