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.
Highlights
Integration of experimental results from multiple species and correlating these with human disease pathology is a multidisciplinary challenge [1]
The proteolytic enzymes used to digest the tissue to single cells, as well as those that are liberated from the tissue, are liable to cleave off antigens, including the very stem cell markers used for FACS-enrichment
In order to determine the cell-of-origin phenotype of breast cancers, we examined the co-expression of the 14 lineage markers in nearly two thousand human breast invasive ductal carcinoma (IDC) samples and found that 95 % of invasive ductal carcinomas have a pure luminal phenotype including ER+, HER2+ and triple negative breast carcinomas (TNBC) [23, 33]
Summary
Integration of experimental results from multiple species and correlating these with human disease pathology is a multidisciplinary challenge [1]. In the case of normal breast stem cell research, this challenge includes correlating results obtained in mouse models with human tissues [2]. The insights gleaned from studying normal cellular lineages must be related to disease states [3, 4]. This integration process has not been always successful, partly due to lack of communication between different fields of research, decreasing number and lack of involvement of CTB experts [1, 5,6,7,8]. We examine some of the factors that contribute to these challenges
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