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Of mice and women: a comparative tissue biology perspective of breast stem cells and differentiation.

Dontu G, Ince TA - J Mammary Gland Biol Neoplasia (2015)

Bottom Line: Tissue based research requires a background in human and veterinary pathology, developmental biology, anatomy, as well as molecular and cellular biology.In addition, we consider the differences between breast ducts vs. lobules and clarify how these affect the interpretation of results in stem cell research.Lastly, we introduce a new elaboration of normal epithelial cell types in human breast and discuss how this provides a clinically useful basis for breast cancer classification.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Group, Breakthrough Breast Cancer Research Unit, Research Oncology, King's College London School of Medicine, 3rd Floor Bermondsey Wing, Guy's Hospital, London, SE1 9RT, UK.

ABSTRACT
Tissue based research requires a background in human and veterinary pathology, developmental biology, anatomy, as well as molecular and cellular biology. This type of comparative tissue biology (CTB) expertise is necessary to tackle some of the conceptual challenges in human breast stem cell research. It is our opinion that the scarcity of CTB expertise contributed to some erroneous interpretations in tissue based research, some of which are reviewed here in the context of breast stem cells. In this article we examine the dissimilarities between mouse and human mammary tissue and suggest how these may impact stem cell studies. In addition, we consider the differences between breast ducts vs. lobules and clarify how these affect the interpretation of results in stem cell research. Lastly, we introduce a new elaboration of normal epithelial cell types in human breast and discuss how this provides a clinically useful basis for breast cancer classification.

No MeSH data available.


Related in: MedlinePlus

Heterogeneity of cell types in human breast. a Double immunostaining of normal human breast section with keratin 5 (red) and smooth muscle actin (SMA, green, FFPE, 400×). b Triple immunostaining of normal human breast section with keratin 5 (blue), estrogen receptor (red), and androgen receptor (green). The cells that co-express ER and AR are yellow (FFPE, 400×). c Triple immunostaining of normal human breast section with keratin 5 (red), keratin 18 (green) and CD10 (white). The cells that co-express K5 and K18 are yellow (FFPE, 400×). d Double-immunostaining of normal human breast section with AR (green) and vitamin-D receptor (red). The cells that co-express AR and VDR are yellow (FFPE, 400×)
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Fig4: Heterogeneity of cell types in human breast. a Double immunostaining of normal human breast section with keratin 5 (red) and smooth muscle actin (SMA, green, FFPE, 400×). b Triple immunostaining of normal human breast section with keratin 5 (blue), estrogen receptor (red), and androgen receptor (green). The cells that co-express ER and AR are yellow (FFPE, 400×). c Triple immunostaining of normal human breast section with keratin 5 (red), keratin 18 (green) and CD10 (white). The cells that co-express K5 and K18 are yellow (FFPE, 400×). d Double-immunostaining of normal human breast section with AR (green) and vitamin-D receptor (red). The cells that co-express AR and VDR are yellow (FFPE, 400×)

Mentions: An important criterion in the selection of the fourteen lineage markers was bimodal expression pattern associated with clear positive and negative cell populations in situ (Fig. 4) [23]. One insight from this study was the impressive heterogeneity of cellular differentiation states in the human breast (Fig. 4) [34]. It is clear that the currently available FACS-based putative stem cell markers that have a gradient type expression in situ (Fig. 2) would be difficult to use for isolating cell subtypes with a bimodal in situ distribution (Fig. 4). Thus, discovery of new stem cell markers with a bimodal in situ distribution is needed in order to correlate stem cell populations with hormonal states. Whether these thirteen cell types represent intermediate differentiation steps within a lineage or define distinct lineages remains to be seen. Other important cell types may yet have to be discovered. However, it is well known that the ligands for ER, AR and VDR are powerful regulators of differentiation and play a critical role in the development of breast tissue. Thus, as opposed to the CD marker based cellular classification, a hormone receptor based differentiation hierarchy might allow us to connect the local, systemic and environmental hormonal cues with cellular lineages and stem cell differentiation.Fig. 4


Of mice and women: a comparative tissue biology perspective of breast stem cells and differentiation.

Dontu G, Ince TA - J Mammary Gland Biol Neoplasia (2015)

Heterogeneity of cell types in human breast. a Double immunostaining of normal human breast section with keratin 5 (red) and smooth muscle actin (SMA, green, FFPE, 400×). b Triple immunostaining of normal human breast section with keratin 5 (blue), estrogen receptor (red), and androgen receptor (green). The cells that co-express ER and AR are yellow (FFPE, 400×). c Triple immunostaining of normal human breast section with keratin 5 (red), keratin 18 (green) and CD10 (white). The cells that co-express K5 and K18 are yellow (FFPE, 400×). d Double-immunostaining of normal human breast section with AR (green) and vitamin-D receptor (red). The cells that co-express AR and VDR are yellow (FFPE, 400×)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig4: Heterogeneity of cell types in human breast. a Double immunostaining of normal human breast section with keratin 5 (red) and smooth muscle actin (SMA, green, FFPE, 400×). b Triple immunostaining of normal human breast section with keratin 5 (blue), estrogen receptor (red), and androgen receptor (green). The cells that co-express ER and AR are yellow (FFPE, 400×). c Triple immunostaining of normal human breast section with keratin 5 (red), keratin 18 (green) and CD10 (white). The cells that co-express K5 and K18 are yellow (FFPE, 400×). d Double-immunostaining of normal human breast section with AR (green) and vitamin-D receptor (red). The cells that co-express AR and VDR are yellow (FFPE, 400×)
Mentions: An important criterion in the selection of the fourteen lineage markers was bimodal expression pattern associated with clear positive and negative cell populations in situ (Fig. 4) [23]. One insight from this study was the impressive heterogeneity of cellular differentiation states in the human breast (Fig. 4) [34]. It is clear that the currently available FACS-based putative stem cell markers that have a gradient type expression in situ (Fig. 2) would be difficult to use for isolating cell subtypes with a bimodal in situ distribution (Fig. 4). Thus, discovery of new stem cell markers with a bimodal in situ distribution is needed in order to correlate stem cell populations with hormonal states. Whether these thirteen cell types represent intermediate differentiation steps within a lineage or define distinct lineages remains to be seen. Other important cell types may yet have to be discovered. However, it is well known that the ligands for ER, AR and VDR are powerful regulators of differentiation and play a critical role in the development of breast tissue. Thus, as opposed to the CD marker based cellular classification, a hormone receptor based differentiation hierarchy might allow us to connect the local, systemic and environmental hormonal cues with cellular lineages and stem cell differentiation.Fig. 4

Bottom Line: Tissue based research requires a background in human and veterinary pathology, developmental biology, anatomy, as well as molecular and cellular biology.In addition, we consider the differences between breast ducts vs. lobules and clarify how these affect the interpretation of results in stem cell research.Lastly, we introduce a new elaboration of normal epithelial cell types in human breast and discuss how this provides a clinically useful basis for breast cancer classification.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Group, Breakthrough Breast Cancer Research Unit, Research Oncology, King's College London School of Medicine, 3rd Floor Bermondsey Wing, Guy's Hospital, London, SE1 9RT, UK.

ABSTRACT
Tissue based research requires a background in human and veterinary pathology, developmental biology, anatomy, as well as molecular and cellular biology. This type of comparative tissue biology (CTB) expertise is necessary to tackle some of the conceptual challenges in human breast stem cell research. It is our opinion that the scarcity of CTB expertise contributed to some erroneous interpretations in tissue based research, some of which are reviewed here in the context of breast stem cells. In this article we examine the dissimilarities between mouse and human mammary tissue and suggest how these may impact stem cell studies. In addition, we consider the differences between breast ducts vs. lobules and clarify how these affect the interpretation of results in stem cell research. Lastly, we introduce a new elaboration of normal epithelial cell types in human breast and discuss how this provides a clinically useful basis for breast cancer classification.

No MeSH data available.


Related in: MedlinePlus