Cytokine Preconditioning Promotes Codifferentiation of Human Fetal Liver CD133
            <sup>+</sup>
            Stem Cells Into Angiomyogenic Tissue

Shmelkov, Sergey V.; Meeus, Sarah; Moussazadeh, Nelson; Kermani, Pouneh; Rashbaum, William K.; Rabbany, Sina Y.; Hanson, Michelle N.; Lane, William J.; Clair, Ryan St; Walsh, Kathryn; Dias, Sérgio; Jacobson, Jason T.; Hempstead, Barbara L.; Edelberg, Jay M.; Rafii, Shahin

doi:10.1161/01.cir.0000157155.44008.0f

Cited by 53 publications

(37 citation statements)

References 38 publications

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“…Purity for CD133 + colon cancer cells from all tumor samples was greater than 97%. 6 ) from each human tumor were injected subcutaneously in the left flank of 3 mice (8 weeks of age). To determine the minimal amount of cells capable of engraftment, we performed limiting dilution experiments.…”

Section: Methodsmentioning

confidence: 99%

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CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

et al. 2008

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Colon cancer stem cells are believed to originate from a rare population of putative CD133 + intestinal stem cells. Recent publications suggest that a small subset of colon cancer cells expresses CD133, and that only these CD133 + cancer cells are capable of tumor initiation. However, the precise contribution of CD133 + tumor-initiating cells in mediating colon cancer metastasis remains unknown. Therefore, to temporally and spatially track the expression of CD133 in adult mice and during tumorigenesis, we generated a knockin lacZ reporter mouse (CD133 lacZ/+ ), in which the expression of lacZ is driven by the endogenous CD133 promoters. Using this model and immunostaining, we discovered that CD133 expression in colon is not restricted to stem cells; on the contrary, CD133 is ubiquitously expressed on differentiated colonic epithelium in both adult mice and humans. Using Il10 -/-CD133 lacZ mice, in which chronic inflammation in colon leads to adenocarcinomas, we demonstrated that CD133 is expressed on a full gamut of colonic tumor cells, which express epithelial cell adhesion molecule (EpCAM). Similarly, CD133 is widely expressed by human primary colon cancer epithelial cells, whereas the CD133 -population is composed mostly of stromal and inflammatory cells. Conversely, CD133 expression does not identify the entire population of epithelial and tumor-initiating cells in human metastatic colon cancer. Indeed, both CD133 + and CD133 -metastatic tumor subpopulations formed colonospheres in in vitro cultures and were capable of long-term tumorigenesis in a NOD/SCID serial xenotransplantation model. Moreover, metastatic CD133 -cells form more aggressive tumors and express typical phenotypic markers of cancer-initiating cells, including CD44 (CD44 + CD24 -), whereas the CD133 + fraction is composed of CD44 low CD24 + cells. Collectively, our data suggest that CD133 expression is not restricted to intestinal stem or cancer-initiating cells, and during the metastatic transition, CD133 + tumor cells might give rise to the more aggressive CD133 -subset, which is also capable of tumor initiation in NOD/SCID mice.

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Section: Methodsmentioning

confidence: 99%

“…Later, it was found on endothelial (4), lymphangiogenic (5), and myoangiogenic (6) progenitors. Although the biological function of CD133 remains unknown, CD133 is recognized as a stem cell marker for normal and cancerous tissues.…”

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confidence: 99%

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

et al. 2008

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“…Among them are mast cells, which increase in number during involution (Qu et al 1995;Tan et al 2004), and myeloid cells (CD45 þ /CD14 þ ), which are present during the proliferative phase. Hemangioma progenitor cells or hemangioma-derived stem cells (HemSCs) have been identified and isolated by us based on the expression of the human stem/progenitor cell marker CD133 (Shmelkov et al 2005). These cells have self-renewal capacity and display multipotential activity, being able to differentiate in vivo into endothelial cells and adipocytes (Khan et al 2008).…”

Section: Mechanism Of Action In Infantile Ihmentioning

confidence: 99%

Infantile Hemangioma--Mechanism(s) of Drug Action on a Vascular Tumor

Greenberger¹,

Bischoff²

2011

Cold Spring Harbor Perspectives in Medicine

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Infantile hemangioma (IH), a benign vascular tumor, is the most common tumor of infancy, with an incidence of 5% -10% at the end of the first year. The tumor displays a distinctive life cycle consisting of a proliferating phase, occurring in the first months of life, followed by an involuting phase. Thus, IH represents a unique model of postnatal vasculogenesis, angiogenesis, and vessel regression. Traditionally, corticosteroids were the drug of choice when treatment of IH was indicated. In recent years, beta-blockers, most specifically propranolol, have serendipitously been shown to be an effective pharmacological treatment. This article will focus on the mechanism of action of these two drugs, the old and the new treatments, in slowing the growth and accelerating involution of IH.

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“…CD133 has been identifed as a pentaspan transmembrane protein in neuroepithelial cells (11) and has been detected in human hematopoietic stem cells (12,13) and several human solid malignancies, such as glioma (5), melanoma (14), osteosarcoma (15) hepatic cancer (16,17), colon cancer (10,18), ovarian cancer (19), and lung cancer (20). A previous report showed that the CD133 + subpopulation in glioma could generate tumors when transplanted into xenogenic immunocompromised mice, and such mice have higher resistance to radiation and chemotherapy (5).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia induces CD133 expression in human lung cancer cells by up-regulation of OCT3/4 and SOX2

Iida

Suzuki

Goitsuka³

et al. 2011

Int J Oncol

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Abstract. CD133 has been recognized as a specific cell surface marker for cancer stem cells in various tumors, although its biological functions and transcriptional regulation remain unclear. We found that the CD133 expression level was up-regulated in the lung cancer cell lines N417, H358, and A549, when these cell lines were cultured under hypoxic conditions. Among the five promoters (P1-P5) of human CD133 gene loci, P1 promoter was most strongly associated with hypoxia-induced promoter activity of CD133 gene expression. The P1 promoter possesses several cis-regulatory elements, including RUNT, GATA, ETS, OCT, SRY, and CREB-binding sites. A series of deletion and base substitution mutants of the P1 promoter revealed that OCT-and SRY-binding sites are important for hypoxia-induced promoter activity. The chromatin immunoprecipitation assay further confirmed the direct binding of Octamer biding transcription factor 3/4 (OCT4) and/or SRY-box containing gene 2 (SOX2) to the P1 promoter region of CD133 gene loci. In addition, the enhancement of both OCT4 and SOX2 expression by the α subunit of hypoxia-inducible factors (HIF1α and HIF2α) was required for hypoxia-induced CD133 expression. Knockdown of OCT4 or SOX2 expression in N417 cells with stabilized HIF1α and/or HIF2α abolished CD133P1 activity, while ectopic OCT4 or SOX2 expression triggers CD133P1 activity in the absence of HIF1α or HIF2α. Thus, in the hypoxic conditions, OCT4 and SOX2, both of which are induced by HIF1α/HIF2α . promote CD133 expression in the lung cancer cells via their direct interaction with the P1 promoter.

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Cytokine Preconditioning Promotes Codifferentiation of Human Fetal Liver CD133 ⁺ Stem Cells Into Angiomyogenic Tissue

Cited by 53 publications

References 38 publications

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

Infantile Hemangioma--Mechanism(s) of Drug Action on a Vascular Tumor

Hypoxia induces CD133 expression in human lung cancer cells by up-regulation of OCT3/4 and SOX2

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Cytokine Preconditioning Promotes Codifferentiation of Human Fetal Liver CD133 + Stem Cells Into Angiomyogenic Tissue

Cited by 53 publications

References 38 publications

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors

Infantile Hemangioma--Mechanism(s) of Drug Action on a Vascular Tumor

Hypoxia induces CD133 expression in human lung cancer cells by up-regulation of OCT3/4 and SOX2

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Cytokine Preconditioning Promotes Codifferentiation of Human Fetal Liver CD133 ⁺ Stem Cells Into Angiomyogenic Tissue