CD9 correlates with cancer stem cell potentials in human B-acute lymphoblastic leukemia cells

Nishida, Hayato; Yamazaki, Hiroto; Yamada, Taketo; Iwata, Satoshi; Dang, Nam H.; Inukai, Takeshi; Sugita, Kanji; Ikeda, Yasuo; Morimoto, Chikao

doi:10.1016/j.bbrc.2009.02.123

Cited by 46 publications

(33 citation statements)

References 19 publications

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“…A similar observation has been recently demonstrated in human B-acute lymphoblastic leukemia cells. 52 Using the NOD/SCID/gc null mouse model, Nishida et al 52 found that transplantation of sorted CD9 ϩ , but not CD9 Ϫ , leukemic cells resulted in tumorigenesis in the bone marrow and spleens of recipients. Another interesting observation was the consistent up-regulation of CD9 expression in CD34 ϩ cells recovered from the bone marrow and spleens of NOD/SCID animals regardless of the CD9 status of the cells originally infused.…”

Section: Discussionmentioning

confidence: 99%

The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood CD34+ hematopoietic stem and progenitor cells

Leung¹,

Chan²,

Ng³

et al. 2011

Blood

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The stromal cell-derived factor-1 (SDF-1)/ chemokine C-X-C receptor 4 (CXCR4) axis plays a critical role in homing and engraftment of hematopoietic stem/progenitor cells (HSCs) during bone marrow transplantation. To investigate the transcriptional regulation provided by this axis, we performed the first differential transcriptome profiling of human cord blood CD34 ؉ cells in response to short-term exposure to SDF-1 and identified a panel of genes with putative homing functions. We demonstrated that CD9, a member of the tetraspanin family of proteins, was expressed in CD34 ؉ CD38 ؊/lo and CD34 ؉ CD38 ؉ cells. CD9 levels were enhanced by SDF-1, which simultaneously down-regulated CXCR4 membrane expression. Using specific inhibitors and activators, we demonstrated that CD9 expression was modulated via CXCR4, G-protein, protein kinase C, phospholipase C, extracellular signalregulated kinase, and Janus kinase 2 signals. Pretreatment of CD34 ؉ cells with the anti-CD9 monoclonal antibody ALB6 significantly inhibited SDF-1-mediated transendothelial migration and calcium mobilization, whereas adhesion to fibronectin IntroductionHoming of hematopoietic stem/progenitor cells (HSCs) to their bone marrow niches is crucial to successful transplantation. This multistep process starts with rolling and tethering of HSCs to bone marrow sinusoidal endothelial cells, followed by migration through the endothelium and extracellular matrix barrier to engage their bone marrow niches. 1,2 The molecular mechanism controlling HSC homing is still not fully understood. Experimental evidence suggests that it requires the orchestrated action of chemokines, 3,4 adhesion molecules, 5,6 and proteolytic enzymes. 7,8 Signaling provided by the interaction of stromal cell-derived factor-1 (SDF-1) with its receptor, chemokine CXC receptor 4 (CXCR4), plays essential roles in regulating HSC homing. Mice lacking SDF-1 or CXCR4 are severely defective in seeding of stem cells in the bone marrow and in the establishment of B-lymphopoiesis and myelopoiesis during development. [9][10][11] In vitro, SDF-1 induces chemotactic and transendothelial migration, 12 adhesion to extracellular matrix proteins under static or shear stress conditions, 5 actin polymerization, 13 and calcium flux 12 in human CD34 ϩ cells. Moreover, homing and engraftment of transplanted CD34 ϩ cells in NOD/ SCID (nonobese diabetic/severe combined immune-deficient) mice are greatly impaired by neutralization of CXCR4 or desensitization by high doses of SDF-1. 3,14 However, CXCR4 Ϫ/Ϫ fetal liver cells are capable (albeit at a lower level) of engraftment in the bone marrow of wild-type mice, 15,16 suggesting that HSC homing and repopulation might not be exclusively controlled by the SDF-1/CXCR4 axis.We previously demonstrated that a short exposure of human cord blood-derived CD34 ϩ cells to a peptide analog of SDF-1 enhances their engraftment in the NOD/SCID mice model. 17 Similarly, others have reported that homing of human or murine HSCs could be significantly improved by pretreatment wit...

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Section: Discussionmentioning

confidence: 99%

The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood CD34+ hematopoietic stem and progenitor cells

Leung¹,

Chan²,

Ng³

et al. 2011

Blood

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“…CD9 is a tetraspanin molecule which plays important roles in cellular development, activation, growth and motility. It has been implicated in a variety of cancers, including but not limited to gastric cancers and B cell acute leukemia [58-60]. …”

Section: Discussionmentioning

confidence: 99%

The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

et al. 2010

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BackgroundThe discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs).MethodsThe ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE) of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established.ResultsWe used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, CD9 and CALM2 mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis.ConclusionThis is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular environment.

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“…We used a four-color flow-cytometry panel to measure the expression of the 28 surface markers in addition to CD44 and CD24 [15, 29, 31, 32, 42–63]. Cells were stained with anti-CD24-AlexaFluor 647 and anti-CD44-PECy7 monoclonal antibodies combined with pairs of antibodies, conjugated with two other different fluorochromes (PE and FITC), directed against the additional surface antigens examined (Additional file 1: Table S1).…”

Section: Methodsmentioning

confidence: 99%

ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells

et al. 2014

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IntroductionTumor-initiating cells (TICs), aka “cancer stem cells”, are believed to fuel tumors and to sustain therapy resistance and systemic metastasis. Breast cancer is the first human carcinoma in which a subpopulation of cells displaying a specific CD44+/CD24-/low/ESA+ antigenic phenotype was found to have TIC properties. However, CD44+/CD24-/low/ESA+ is not a universal marker phenotype of TICs in all breast cancer subtypes. The aim of this study was to identify novel antigens with which to isolate the TIC population of the basal-A/basal-like breast cancer cell lines.MethodsWe used polychromatic flow-cytometry to characterize the cell surface of several breast cancer cell lines that may represent different tumor molecular subtypes. We next used fluorescence-activated cell sorting to isolate the cell subpopulations of interest from the cell lines. Finally, we explored the stem-like and tumorigenic properties of the sorted cell subpopulations using complementary in vitro and in vivo approaches: mammosphere formation assays, soft-agar colony assays, and tumorigenic assays in NOD/SCID mice.ResultsThe CD44+/CD24+ subpopulation of the BRCA1-mutated basal-A/basal-like cell line HCC1937 is enriched in several stemness markers, including the ABCG2 transporter (i.e., the CD338 antigen). Consistently, CD338-expressing cells were also enriched in CD24 expression, suggesting that coexpression of these two antigenic markers may segregate TICs in this cell line. In support of ABCG2 expression in TICs, culturing of HCC1937 cells in ultra-low adherent conditions to enrich them in precursor/stem-cells resulted in an increase in CD338-expressing cells. Furthermore, CD338-expressing cells, unlike their CD338-negative counterparts, displayed stemness and transformation potential, as assessed in mammosphere and colony formation assays. Lastly, CD338-expressing cells cultured in ultra-low adherent conditions maintained the expression of CD326/EpCAM and CD49f/α6-integrin, which is a combination of antigens previously assigned to luminal progenitors.ConclusionCollectively, our data suggest that CD338 expression is specific to the tumor-initiating luminal progenitor subpopulation of BRCA1-mutated cells and is a novel antigen with which to sort this subpopulation.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-213) contains supplementary material, which is available to authorized users.

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CD9 correlates with cancer stem cell potentials in human B-acute lymphoblastic leukemia cells

Cited by 46 publications

References 19 publications

The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood CD34+ hematopoietic stem and progenitor cells

The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood CD34+ hematopoietic stem and progenitor cells

The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells

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