Human Uterine Leiomyoma Stem/Progenitor Cells Expressing CD34 and CD49b Initiate Tumors In Vivo

Yin, Ping; Ono, Masanori; Moravek, Molly B.; Coon, John S.; Navarro, Antònia; Monsivais, Diana; Dyson, Matthew T.; Druschitz, Stacy A.; Malpani, Saurabh S.; Serna, Vanida A.; Qiang, Wenan; Chakravarti, Debabrata; Kim, Julie; Bulun, Serdar E.

doi:10.1210/jc.2014-2134

Cited by 74 publications

(85 citation statements)

References 20 publications

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“…Interestingly, CD34+/CD49b- cells had intermediate levels of these stem cell factors compared to CD34-/CD49b- cells. Additionally, ER-alpha and PR were significantly underexpressed in CD34+/CD49b+ cells, consistent with prior studies on SP, and CD34+/CD49b- cells again showed intermediate expression levels between CD34+/CD49b+ and CD34-/CD49b- cells[78**]. Taken together, these results led us to hypothesize that CD34+/CD49b+ cells are largely fibroid somatic stem cells, capable of asymmetric division allowing both self-renewal and the production of intermediary daughter cells, or CD34+/CD49b-cells, which ultimately develop into fully differentiated fibroid cells, or CD34-/CD49b- cells.…”

Section: Somatic Stem Cellssupporting

confidence: 89%

“…Originally, fibroid stem cells were isolated using the Hoechst dye exclusion technique for side populations (SP)[75, 76], however, the SP technique is expensive, exhibits significant sensitivity to minor staining variations, and is detrimental to cell survival, making further study of fibroid cells difficult[77]. As a solution to these pitfalls, we recently reported a novel way of isolating fibroid stem cells using cell surface markers CD34 and CD49b[78**]. Cell sorting using antibodies to these cell surface proteins revealed 3 distinct cell populations: CD34+/CD49b+, CD34+/CD49b-, and CD34-/CD49b- cells (figure 2).…”

Section: Somatic Stem Cellsmentioning

confidence: 99%

“…CD34+/CD49b+ cells were highly enriched with stem cells whereas the other two groups did not contain any stem cells. Moreover, genes specific to stem cells, such as KLF4, NANOG, OCT4 were overexpressed in the CD34+/CD49b+ cells further suggesting that these cells are indeed stem cells[78**]. Interestingly, CD34+/CD49b- cells had intermediate levels of these stem cell factors compared to CD34-/CD49b- cells.…”

Section: Somatic Stem Cellsmentioning

confidence: 99%

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Endocrinology of uterine fibroids

Moravek

Bulun

2015

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of Review Uterine fibroids are extremely common, and can cause significant morbidity, yet the exact etiology of these tumors remains elusive and there are currently no long-term treatments available. In this review we aim to provide an overview of steroid hormones, genetic abnormalities, and stem cells in the pathogenesis of uterine fibroids. Recent Findings A universal feature of fibroids is responsiveness to estrogen and progesterone, and most of the currently available therapies exploit this characteristic. Ulipristal acetate has recently shown particular promise for providing long-term relief from uterine fibroids. Additionally, fibroid stem cells were isolated and appear to be necessary for growth. The recent discovery of somatic mutations involving MED12 or HMGA2 in the majority of fibroids and the links to their pathophysiology were also significant advances. Summary The recent shift in focus from hormones to fibroid stem cells and genetic aberrations should lead not only to a deeper understanding of the specific etiology of fibroids, but also to the discovery of new therapeutic targets. Targeting the products of genetic mutations or fibroid stem cells has the potential to achieve both better control of current tumors and the prevention of new fibroids.

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Section: Somatic Stem Cellssupporting

confidence: 89%

Section: Somatic Stem Cellsmentioning

confidence: 99%

Section: Somatic Stem Cellsmentioning

confidence: 99%

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Endocrinology of uterine fibroids

Moravek

Bulun

2015

Current Opinion in Obstetrics &Amp; Gynecology

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“…Recently, it was shown that human uterine leiomyoma stem/progenitor cells expressed CD34 and CD49b, which initiate tumors in vivo …”

Section: Introductionmentioning

confidence: 99%

“…5 Recently, it was shown that human uterine leiomyoma stem/progenitor cells expressed CD34 and CD49b, which initiate tumors in vivo. 6 Pathological alterations of signaling pathways have been recognized as a key feature in a variety of human diseases. 7 The successful development of protein tyrosine kinase inhibitors (PTK) has suggested them as candidates for 'signal transduction therapy'.…”

Section: Introductionmentioning

confidence: 99%

Targeting leiomyomas with all‐trans‐retinoic acid at phosphoinositide 3‐kinase pathway suppression: Effective roles of β‐catenin and of signaling interactions

Friedman

Shushan

Rojansky

et al. 2016

J of Obstet and Gynaecol

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ATRA treatment on PI3K pathway suppression significantly affected growth, signaling pattern and interactions among PI3K/Bcl2/retinol proteins involved in the growth, survival and apoptosis of leiomyomas. Interpretation of our results suggests that increasing knowledge of the role of signaling interplay in the pathogenesis of leiomyomas may present an opportunity to use specific signal transduction inhibitors for treating and preventing this disorder.

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CD34 cells in somatic, regenerative and cancer stem cells: Developmental biology, cell therapy, and omics big data perspective

Kapoor

Bose

2019

J of Cellular Biochemistry

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The transmembrane phosphoglycoprotein protein CD34 has conventionally been regarded as a marker for hematopoietic progenitors. Its expression on these cells has been leveraged for cell therapy applications in various hematological disorders. More recently, the expression of CD34 has also been reported on cells of nonhematopoietic origin. The list includes somatic cells such as endothelial cells, fibrocytes and interstitial cells and regenerative stem cells such as corneal keratocytes, muscle satellite cells, and muscle-derived stem cells. Furthermore, its expression on some cancer stem cells (CSCs) has also been reported. Till date, the functional roles of this molecule have been implicated in a multitude of cellular processes including cell adhesion, signal transduction, and maintenance of progenitor phenotype. However, the complete understanding about this molecule including its developmental origins, its embryonic connection, and associated functions is far from complete. Here, we review our present understanding of the structure and putative functions of the CD34 molecule based upon our literature survey. We also probed various biological databases to retrieve data related to the expression and associated molecular functions of CD34. Such information, upon synthesis, is hence likely to provide the suitability of such cells for cell therapy.Moreover, we have also covered the existing cell therapy and speculated cell therapy applications of CD34 + cells isolated from various lineages. We have also attempted here to speculate the role(s) of CD34 on CSCs. Finally, we discuss number of large-scale proteomics and transcriptomics studies that have been performed using CD34 + cells.

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Human Uterine Leiomyoma Stem/Progenitor Cells Expressing CD34 and CD49b Initiate Tumors In Vivo

Abstract: CD34 and CD49b are cell surface markers that can be used to enrich a subpopulation of leiomyoma cells possessing stem/progenitor cell properties; this technique will accelerate efforts to develop new therapies for uterine leiomyoma.

Cited by 74 publications

References 20 publications

Endocrinology of uterine fibroids

Endocrinology of uterine fibroids

Targeting leiomyomas with all‐trans‐retinoic acid at phosphoinositide 3‐kinase pathway suppression: Effective roles of β‐catenin and of signaling interactions

CD34 cells in somatic, regenerative and cancer stem cells: Developmental biology, cell therapy, and omics big data perspective

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