Mammary gland stem cells: More puzzles than explanations

Kaimala, Suneesh; Bisana, Swathi; Kumar, Satish

doi:10.1007/s12038-012-9200-z

Cited by 11 publications

(4 citation statements)

References 66 publications

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“…However, NANOG is a particularly challenging therapeutic target given its role as a master transcription factor important in several cellular functions in CSC and non-cancer stem cells, including adipose-derived and mammary gland stem cells (Dentelli, et al 2012; Kaimala, et al 2012). Our novel findings of the inhibitory effects of LEPR silencing on NANOG expression, CSC self-renewal, cell proliferation, and tumor outgrowth in murine and human breast cancer cell lines suggest LEPR or components of its downstream signaling pathway may be promising as a druggable targets to inhibit the pro-cancer effects associated with NANOG .…”

Section: Discussionmentioning

confidence: 99%

Leptin receptor maintains cancer stem-like properties in triple negative breast cancer cells

Zheng

Banaszak

Fracci

et al. 2013

Endocrine-Related Cancer

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Despite new therapies, breast cancer continues to be the second leading cause of cancer mortality in women a consequence of recurrence and metastasis. In recent years, a population of cancer cells has been identified, called cancer stem cells (CSCs) with self-renewal capacity, proposed to underlie tumor recurrence and metastasis. We previously showed that the adipose tissue cytokine LEPTIN, increased in obesity, promotes the survival of CSCs in vivo. Here, we tested the hypothesis that the Leptin Receptor (LEPR), expressed in mammary cancer cells, is necessary for maintaining CSC-like and metastatic properties. We silenced LEPR via shRNA lentivirus transduction and determined that expression of stem cell self-renewal transcription factors NANOG, SOX2, and OCT4 are inhibited. LEPR-NANOG signaling pathway is conserved between species because we can rescue NANOG expression in human LEPR-silenced cells with the mouse LepR. Using a NANOG promoter GFP reporter, we showed that LEPR is enriched in NANOG promoter active (GFP+) cells. Using lineage tracing, we showed that the GFP+ cells exhibit symmetric and asymmetric division and cell death. LEPR silenced MDA-MB-231 cells exhibit a mesenchymal to epithelial transition morphologically, increased E-CADHERIN and decreased VIMENTIN expression compared to control cells. Finally, LEPR silenced cells exhibit reduced cell proliferation, self-renewal in tumorsphere assays, and tumor outgrowth in xenotransplant studies. Given the emergence of NANOG as a pro-carcinogenic protein in multiple cancers, these studies suggest that inhibition of LEPR may be a promising therapeutic approach to inhibit NANOG and thereby neutralize CSC functions.

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Section: Discussionmentioning

confidence: 99%

Leptin receptor maintains cancer stem-like properties in triple negative breast cancer cells

Zheng

Banaszak

Fracci

et al. 2013

Endocrine-Related Cancer

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“…While there is a general consensus about some of the factors that mark and or regulate the MaSC population, the field has been left with more questions than answers when trying to specifically define MaSCs [74]. For example, the estimates for stem cell frequency, derived from calculating the number of mammary repopulating units, varies dramatically.…”

Section: The Mammary Stem Cell Conundrum: More Questions Than Ansmentioning

confidence: 99%

Unraveling Heterogeneity in Epithelial Cell Fates of the Mammary Gland and Breast Cancer

Samocha

Doh

Kessenbrock

et al. 2019

Cancers

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Fluidity in cell fate or heterogeneity in cell identity is an interesting cell biological phenomenon, which at the same time poses a significant obstacle for cancer therapy. The mammary gland seems a relatively straightforward organ with stromal cells and basal- and luminal- epithelial cell types. In reality, the epithelial cell fates are much more complex and heterogeneous, which is the topic of this review. Part of the complexity comes from the dynamic nature of this organ: the primitive epithelial tree undergoes extensively remodeling and expansion during puberty, pregnancy, and lactation and, unlike most other organs, the bulk of mammary gland development occurs late, during puberty. An active cell biological debate has focused on lineage commitment to basal- and luminal- epithelial cell fates by epithelial progenitor and stem cells; processes that are also relevant to cancer biology. In this review, we discuss the current understanding of heterogeneity in mammary gland and recent insights obtained through lineage tracing, signaling assays, and organoid cultures. Lastly, we relate these insights to cancer and ongoing efforts to resolve heterogeneity in breast cancer with single-cell RNAseq approaches.

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“…In addition, researchers have reported MaSCs as bi-potent [14] and lineage-restricted unipotent stem cells [6]. Indeed, the precise identification and subsequent characterization of MaSCs are conflicting [15] and need to be re-evaluated in the context of their dynamics [16]. Identifying different MaSC subtypes will allow precise targets to be found for optimal manipulation of increased milk production.…”

Section: Reviewmentioning

confidence: 99%

Mammary stem cells: expansion and animal productivity

Choudhary

2014

J Animal Sci Biotechnol

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Identification and characterization of mammary stem cells and progenitor cells from dairy animals is important in the understanding of mammogenesis, tissue turnover, lactation persistency and regenerative therapy. It has been realized by many investigators that altered lactation, long dry periods (non-milking period between two consecutive lactation cycles), abrupt cessation of lactation (common in water buffaloes) and disease conditions like mastitis, greatly reduce milk yield thus render huge financial losses within the dairy sector. Cellular manipulation of specialized cell types within the mammary gland, called mammary stem cells (MaSCs)/progenitor cells, might provide potential solutions to these problems and may improve milk production. In addition, MaSCs/progenitor cells could be used in regenerative therapy against tissue damage caused by mastitis. This review discusses methods of MaSC/progenitor cell manipulation and their mechanisms in bovine and caprine animals. Author believes that intervention of MaSCs/progenitor cells could lessen the huge financial losses to the dairy industry globally.

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Mammary gland stem cells: More puzzles than explanations

Cited by 11 publications

References 66 publications

Leptin receptor maintains cancer stem-like properties in triple negative breast cancer cells

Leptin receptor maintains cancer stem-like properties in triple negative breast cancer cells

Unraveling Heterogeneity in Epithelial Cell Fates of the Mammary Gland and Breast Cancer

Mammary stem cells: expansion and animal productivity

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