Membrane-bound stem cell factor is a key regulator in the initial lodgment of stem cells within the endosteal marrow region

Driessen, Rebecca; Johnston, Hayley M.; Nilsson, Susan K.

doi:10.1016/j.exphem.2003.08.015

Cited by 122 publications

(92 citation statements)

References 47 publications

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“…It localises to the cell membrane, where the isoform that includes exon 6 can undergo proteolytic cleavage of the extracellular domain to release soluble SCF. The isoform that lacks exon 6 cannot be cleaved and remains membrane bound (Miyazawa et al, 1995;Gommerman et al, 2000;Driessen et al, 2003). The soluble form of SCF rapidly activates c-Kit but the signalling activity quickly decays owing to receptor internalisation.…”

Section: Discussionmentioning

confidence: 99%

“…The membrane bound form gives a more persistent signalling activity, possibly owing to increased stability of the receptor-ligand complex and reduced internalisation (Miyazawa et al, 1995;Gommerman et al, 1997). In vivo, only the membrane bound form supports survival of long-term haematopoietic progenitors (Gommerman et al, 2000;Driessen et al, 2003). The Steel-Dickie mutation in mice generates an SCF protein lacking both transmembrane and cytoplasmic domains and results in production of only soluble SCF (Brannan et al, 1991), supporting the importance of the membrane bound form in a number of biological processes.…”

Section: Discussionmentioning

confidence: 99%

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c-Kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer

et al. 2011

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BRCA1 mutation-associated breast cancer originates in oestrogen receptor-alpha-negative (ER À ) progenitors in the mammary luminal epithelium. These cells also express high levels of the Kit gene and a recent study demonstrated a correlation between Brca1 loss and Kit over-expression in the mammary epithelium. However, the functional significance of c-Kit expression in the mammary gland is unknown. To address this, c-Kit À and c-Kit þ mammary epithelial subsets were isolated by flow cytometry, characterised for expression of lineage-specific cell markers and functionally analysed by in vitro colony forming and in vivo transplantation assays. The results confirm that the majority of luminal ER À progenitors are c-Kit þ , but also that most stem cells and the differentiated cell populations are c-Kit À . A subset of c-Kit þ cells with high proliferative potential was found in the luminal ER þ population, however, suggesting the existence of a distinct luminal ER þ progenitor cell type. Analysis of mouse Brca1 mammary tumours demonstrated that they expressed Kit and its downstream effector Lyn at levels comparable to the most strongly c-Kit þ luminal ER À progenitors. Consistent with c-Kit being a progenitor cell marker, in vitro threedimensional differentiation of c-Kit þ cells resulted in a loss of c-Kit expression, whereas c-Kit over-expression prevented normal differentiation in vivo. Furthermore, c-Kit was a functional marker of proliferative potential, as c-Kit inhibition by short hairpin knockdown prevented normal epithelial growth and caused cells to undergo apoptosis. Therefore, c-Kit defines distinct progenitor populations in the mammary epithelium and is critical for mammary progenitor survival and proliferation. Importantly, c-Kit is only the second mammary epithelial stem/progenitor marker to be shown to have a functional role in the mammary epithelium and the first marker to be shown to be required for progenitor cell function. The c-Kit signalling network has potential as a target for therapy and/or prevention in BRCA1-associated breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

c-Kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer

et al. 2011

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“…9,20 Our recent studies demonstrate that HA, like Opn also acts as a negative regulator to promote HSC quiescence. In Stem Cell Regulation by the Hemopoietic Stem Cell Niche Figure 1.…”

Section: Introductionmentioning

confidence: 99%

“…Other stromal and microenvironmental cell types and their extracellular matrix proteins also contribute to this biology. For example, the glycosaminoglycan hyaluronic acid (HA), 9 as well as the membrane bound form of the cytokine stem cell factor (mSCF) 20 are also key components of the HSC niche.…”

Section: Introductionmentioning

confidence: 99%

Stem Cell Regulation by the Haemopoietic Stem Cell Niche

Haylock¹,

Nilsson²

2005

Cell Cycle

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“…Many proteins including Sca-1, c-Kit, CD34, and urokinase-type plasminogen activator receptor (uPAR; CD87) have been identified as regulators of HSPC adhesion to osteoblastic niches (12)(13)(14)(15)(16)(17). In fact, recent studies using overexpressing or knock-out mice and cells for angiopoietin-1, thrombopoietin, bone morphogenetic protein-4, Secreted frizzled related protein-1 (Sfrp-1), or uPAR have shown that changes in expression of the respective gene cause disturbed maintenance of normal HSPC pool size and lead to pathological conditions typical of hematological proliferative disease or severe anemia (2).…”

mentioning

confidence: 99%

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

Nishii

Nakaseko

Jiang

et al. 2013

Journal of Biological Chemistry

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Background: Serum levels of the soluble LR11 fragment (sLR11) increase in patients with acute leukemia. Results: Hypoxia-induced factor (HIF)-1␣ activation increases LR11 levels, and sLR11 enhances adhesion of HSPCs to BM stromal cells via a uPAR-mediated pathway. Conclusion: sLR11 regulates hypoxia-induced attachment of HSPCs. Significance: sLR11 may stabilize the hematological pool size by controlling HSPC attachment to the BM niche.

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Membrane-bound stem cell factor is a key regulator in the initial lodgment of stem cells within the endosteal marrow region

Cited by 122 publications

References 47 publications

c-Kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer

c-Kit is required for growth and survival of the cells of origin of Brca1-mutation-associated breast cancer

Stem Cell Regulation by the Haemopoietic Stem Cell Niche

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

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