Imaging of cell trafficking and metastases of paediatric rhabdomyosarcoma

Seitz, Guido; Warmann, Steven W.; Fuchs, Joerg; Heitmann, Heike; Mahrt, J.; Busse, Ann-Christin; Ruck, Peter; Hoffman, Robert M.; Wessels, Johannes T.

doi:10.1111/j.1365-2184.2008.00520.x

Cited by 18 publications

(15 citation statements)

References 17 publications

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“…It is possible that the pattern of intracellular distribution of TdTom may depend on the cell type. Indeed, the localization of TdTom varies according to the cell type [29], and DsRed2, another type of RFP, shows dotted pattern in cells derived from rhabdomyosarcoma [30].…”

Section: Discussionmentioning

confidence: 99%

Stem Cell-Like Differentiation Potentials of Endometrial Side Population Cells as Revealed by a Newly Developed In Vivo Endometrial Stem Cell Assay

et al. 2012

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BackgroundEndometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP), but not endometrial main population cells (EMP), exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche) to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay.Methodology/Principal FindingsESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom), a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells.Conclusions/SignificanceWe have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo endometrial tissue reconstitution. Using this assay, we demonstrated that ESP cells differentiated into multiple endometrial lineages in the niche provided by whole endometrial cells, indicating that ESP cells are genuine endometrial stem/progenitor cells.

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Section: Discussionmentioning

confidence: 99%

Stem Cell-Like Differentiation Potentials of Endometrial Side Population Cells as Revealed by a Newly Developed In Vivo Endometrial Stem Cell Assay

et al. 2012

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“…In larger vessels, tumor cells attached to the vessel walls and an extravasation was observed 12 h later. The study concluded that the experimental metastatic invasion of rhabdomyosarcoma cells was caused by tumor cell accumulation and extravasation (45).…”

Section: Optical Imaging (Fluorescent Proteins)mentioning

confidence: 99%

Animal models of extracranial pediatric solid tumors

et al. 2012

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Abstract. Animal models, including xenografts, models of metastatic invasion, syngeneic models and transgenic models, are important tools for basic research in solid pediatric tumors, while humanized animal models are useful for novel immunotherapeutical approaches. Optical and molecular imaging techniques are used for in vivo imaging and may be used in conjunction with alternative treatment approaches, including photodynamic therapy. The aim of this review is to highlight the various animal models that may be used for basic research in pediatric solid tumors.

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“…For these studies, the infrared-fluorescent protein FP635 (mKATE) was cloned into the sneaking ligand constructs for their visualization (29,30). We examined the uptake of SLC1-FP635 into CHO_E cells by immunofluorescence microscopy.…”

Section: Nf-κb Inhibition Via E-selectin-mediated Endocytosis Of Slc1mentioning

confidence: 99%

“…In vivo imaging was used to prove the selective binding of SLC1 to cytokine-activated but not to resting endothelium in vivo (29,30). An epigastric vein in a cytokine-induced skin flap of live transgenic green fluorescent protein (GFP)-expressing mice was selected as the region of interest for SLC1 detection (Fig.…”

Section: Nf-κb Inhibition Via E-selectin-mediated Endocytosis Of Slc1mentioning

confidence: 99%

NF-κB inhibitor targeted to activated endothelium demonstrates a critical role of endothelial NF-κB in immune-mediated diseases

Sehnert

Burkhardt

Wessels

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Activation of the nuclear transcription factor κB (NF-κB) regulates the expression of inflammatory genes crucially involved in the pathogenesis of inflammatory diseases. NF-κB governs the expression of adhesion molecules that play a pivotal role in leukocyteendothelium interactions. We uncovered the crucial role of NF-κB activation within endothelial cells in models of immune-mediated diseases using a "sneaking ligand construct" (SLC) selectively inhibiting NF-κB in the activated endothelium. The recombinant SLC1 consists of three modules: (i) an E-selectin targeting domain, (ii ) a Pseudomonas exotoxin A translocation domain, and (iii) a NF-κB Essential Modifier-binding effector domain interfering with NF-κB activation. The E-selectin-specific SLC1 inhibited NF-κB by interfering with endothelial IκB kinase 2 activity in vitro and in vivo. In murine experimental peritonitis, the application of SLC1 drastically reduced the extravasation of inflammatory cells. Furthermore, SLC1 treatment significantly ameliorated the disease course in murine models of rheumatoid arthritis. Our data establish that endothelial NF-κB activation is critically involved in the pathogenesis of arthritis and can be selectively inhibited in a cell type-and activation stage-dependent manner by the SLC approach. Moreover, our strategy is applicable to delineating other pathogenic signaling pathways in a cell type-specific manner and enables selective targeting of distinct cell populations to improve effectiveness and riskbenefit ratios of therapeutic interventions.cell targeting | intracellular signaling | autoimmune disorders | mouse models | inhibit inflammation A critical step in the effector phase of pathogenic immune responses is the extravasation of circulating leukocytes from the vasculature and their migration along gradients of chemoattractants into the target tissues (1). In inflammation, endothelial activation represents a multistep cascade of events leading to increased vascular permeability for plasma proteins; the expression of proinflammatory cytokines, chemokines, and enzymes; and an up-regulation of adhesion molecules that are regulated by the nuclear transcription factor κB (NF-κB) (2-4).Activation of NF-κB via the IκB kinase (IKK) complex is regarded as the classical NF-κB pathway. The IKK complex contains the kinases IKK1 and IKK2 and the regulatory subunit NF-κB Essential Modifier (NEMO) (5). Activation of the classical NF-κB pathway requires association of NEMO with IKK2 (5). The expression of multiple proinflammatory genes including the adhesion molecules ICAM-1, VCAM-1, E-selectin, and chemokines, like MCP-1 and IL-8, contributes to the inflammatory endothelial cell response and is initiated through activation of the classical NF-κB pathway (6).

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Imaging of cell trafficking and metastases of paediatric rhabdomyosarcoma

Cited by 18 publications

References 17 publications

Stem Cell-Like Differentiation Potentials of Endometrial Side Population Cells as Revealed by a Newly Developed In Vivo Endometrial Stem Cell Assay

Stem Cell-Like Differentiation Potentials of Endometrial Side Population Cells as Revealed by a Newly Developed In Vivo Endometrial Stem Cell Assay

Animal models of extracranial pediatric solid tumors

NF-κB inhibitor targeted to activated endothelium demonstrates a critical role of endothelial NF-κB in immune-mediated diseases

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