共查询到20条相似文献,搜索用时 31 毫秒
1.
Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research 总被引:1,自引:1,他引:0
Han ME Jeon TY Hwang SH Lee YS Kim HJ Shim HE Yoon S Baek SY Kim BS Kang CD Oh SO 《Cellular and molecular life sciences : CMLS》2011,68(21):3589-3605
Cancer stem cells have been hypothesized to drive the growth and metastasis of tumors. Because they need to be targeted for cancer treatment, they have been isolated from many solid cancers. However, cancer stem cells from primary human gastric cancer tissues have not been isolated as yet. For the isolation, we used two cell surface markers: the epithelial cell adhesion molecule (EpCAM) and CD44. When analyzed by flow cytometry, the EpCAM+/CD44+ population accounts for 4.5% of tumor cells. EpCAM+/CD44+ gastric cancer cells formed tumors in immunocompromised mice; however, EpCAM?/CD44?, EpCAM+/CD44? and EpCAM?/CD44+ cells failed to do so. Xenografts of EpCAM+/CD44+ gastric cancer cells maintained a differentiated phenotype and reproduced the morphological and phenotypical heterogeneity of the original gastric tumor tissues. The tumorigenic subpopulation was serially passaged for several generations without significant phenotypic alterations. Moreover, EpCAM+/CD44+, but not EpCAM?/CD44?, EpCAM+/CD44? or EpCAM?/CD44+ cells grew exponentially in vitro as cancer spheres in serum-free medium, maintaining the tumorigenicity. Interestingly, a single cancer stem cell generated a cancer sphere that contained various differentiated cells, supporting multi-potency and self-renewal of a cancer stem cell. EpCAM+/CD44+ cells had greater resistance to anti-cancer drugs than other subpopulation cells. The above in vivo and in vitro results suggest that cancer stem cells, which are enriched in the EpCAM+/CD44+ subpopulation of gastric cancer cells, provide an ideal model system for cancer stem cell research. 相似文献
2.
Koninckx R Daniëls A Windmolders S Carlotti F Mees U Steels P Rummens JL Hendrikx M Hensen K 《Cellular and molecular life sciences : CMLS》2011,68(12):2141-2156
In the past, clinical trials transplanting bone marrow–derived mononuclear cells reported a limited improvement in cardiac
function. Therefore, the search for stem cells leading to more successful stem cell therapies continues. Good candidates are
the so-called cardiac stem cells (CSCs). To date, there is no clear evidence to show if these cells are intrinsic stem cells
from the heart or mobilized cells from bone marrow. In this study we performed a comparative study between human mesenchymal
stem cells (hMSCs), purified c-kit+ CSCs, and cardiosphere-derived cells (CDCs). Our results showed that hMSCs can be discriminated from CSCs by their differentiation
capacity towards adipocytes and osteocytes and the expression of CD140b. On the other hand, cardiac progenitors display a
greater cardiomyogenic differentiation capacity. Despite a different isolation protocol, no distinction could be made between
c-kit+ CSCs and CDCs, indicating that they probably derive from the same precursor or even are the same cells. 相似文献
3.
Natascha Cremers Marie-Ange Deugnier Jonathan Sleeman 《Cellular and molecular life sciences : CMLS》2010,67(13):2311-2322
CD24 is expressed on mammary stem cells and is used as a marker for their isolation, yet its function in the mammary gland
still needs to be examined. Here we show that CD24 is expressed throughout the luminal epithelial cell layer, but only weakly
in myoepithelial cells. During lactation, CD24 expression was suppressed within alveoli, but upregulated post-lactation, returning
to a pre-pregnant spatial distribution. CD24-deficient mice exhibited an accelerated mammary gland ductal extension during
puberty and an enhanced branching morphogenesis, resulting in increased furcation in the ductal structure. CD24−/− mammary
epithelial cells were able to completely repopulate cleared mammary fat pads and to give rise to fully functional mammary
glands. Together, these data suggest that while CD24 is expressed in mammary epithelium compartments thought to contain stem
cells, CD24 is not a major regulator of mammary stem/progenitor cell function, but rather plays a role in governing branching
morphogenesis. 相似文献
4.
Yvonne G. J. van Helden Roger W. L. Godschalk Hans J. M. Swarts Peter C. H. Hollman Frederik J. van Schooten Jaap Keijer 《Cellular and molecular life sciences : CMLS》2011,68(3):489-504
Molecular mechanisms triggered by high dietary beta-carotene (BC) intake in lung are largely unknown. We performed microarray
gene expression analysis on lung tissue of BC supplemented beta-carotene 15,15′-monooxygenase 1 knockout (Bcmo1
−/−) mice, which are—like humans—able to accumulate BC. Our main observation was that the genes were regulated in an opposite direction in male and female Bcmo1
−/− mice by BC. The steroid biosynthetic pathway was overrepresented in BC-supplemented male Bcmo1
−/− mice. Testosterone levels were higher after BC supplementation only in Bcmo1
−/− mice, which had, unlike wild-type (Bcmo1
+/+) mice, large variations. We hypothesize that BC possibly affects hormone synthesis or metabolism. Since sex hormones influence
lung cancer risk, these data might contribute to an explanation for the previously found increased lung cancer risk after
BC supplementation (ATBC and CARET studies). Moreover, effects of BC may depend on the presence of frequent human BCMO1 polymorphisms, since these effects were not found in wild-type mice. 相似文献
5.
D. Parolini M. Meregalli M. Belicchi P. Razini R. Lopa B. Del Carlo A. Farini S. Maciotta N. Bresolin L. Porretti M. Pellegrino Y. Torrente 《Cellular and molecular life sciences : CMLS》2009,66(4):697-710
Among the heterogeneous population of circulating hematopoietic and endothelial progenitors, we identified a subpopulation
of CD133+ cells displaying myogenic properties. Unexpectedly, we observed the expression of the B-cell marker CD20 in blood-derived
CD133+ stem cells. The CD20 antigen plays a role in the modulation of intracellular calcium homeostasis through signaling pathways
activation. Several observations suggest that an increase in intracellular calcium concentration ([Ca2+]i) could be involved in the etiology of the Duchenne muscular dystrophy (DMD). Here, we show that a CD20-related signaling
pathway able to induce an increase in [Ca2+]i is differently activated after brain derived neurotrophic factor (BDNF) stimulation of normal and dystrophic blood-derived
CD133+ stem cells, supporting the assumption of a “CD20-related calcium impairment-affecting dystrophic cells. Presented findings
represent the starting point toward the expansion of knowledge on pathways involved in the pathology of DMD and in the behavior
of dystrophic blood-derived CD133+ stem cells.
Received 15 October 2008; received after revision 27 November 2008; accepted 05 December 2008 相似文献
6.
Characterization of murine non-adherent bone marrow cells leading to recovery of endogenous hematopoiesis 总被引:1,自引:1,他引:0
Stephan Fricke Christian Fricke Christopher Oelkrug Nadja Hilger Uta Sch?nfelder Manja Kamprad J?rg Lehmann Johannes Boltze Frank Emmrich Ulrich Sack 《Cellular and molecular life sciences : CMLS》2010,67(23):4095-4106
Non-adherent bone marrow-derived cells (NA-BMCs) are a mixed cell population that can give rise to multiple mesenchymal phenotypes
and that facilitates hematopoietic recovery. We characterized NA-BMCs by flow cytometry, fibroblast colony-forming units (CFU-f),
real-time PCR, and in in vivo experiments. In comparison to adherent cells, NA-BMCs expressed high levels of CD11b+ and CD90+ within the CD45+ cell fraction. CFU-f were significantly declining over the cultivation period, but NA-BMCs were still able to form CFU-f
after 5 days. Gene expression analysis of allogeneic NA-BMCs compared to bone marrow (BM) indicates that NA-BMCs contain stromal,
mesenchymal, endothelial cells and monocytes, but less osteoid, lymphoid, and erythroid cells, and hematopoietic stem cells.
Histopathological data and analysis of weight showed an excellent recovery and organ repair of lethally irradiated mice after
NA-BMC transplantation with a normal composition of the BM. 相似文献
7.
8.
Tsai S Clemente-Casares X Santamaria P 《Cellular and molecular life sciences : CMLS》2011,68(23):3781-3795
Autoreactive CD8+ regulatory T cells (Tregs) play important roles as modulators of immune responses against self, and numerical and functional
defects in CD8+ Tregs have been linked to autoimmunity. Several subsets of CD8+ Tregs have been described. However, the origin of these T cells and how they participate in the natural progression of autoimmunity
remain poorly defined. We discuss several lines of evidence suggesting that the autoimmune process itself promotes the development
of autoregulatory CD8+ T cells. We posit that chronic autoantigenic exposure fosters the differentiation of non-pathogenic autoreactive CD8+ T cells into antigen-experienced, memory-like autoregulatory T cells, to generate a “negative feedback” regulatory loop capable
of countering pathogenic autoreactive effectors. This hypothesis predicts that approaches capable of boosting autoregulatory
T cell memory will be able to blunt autoimmunity without compromising systemic immunity. 相似文献
9.
Julie Patenaude Michele D’Elia Claudine Hamelin Jacques Bernier 《Cellular and molecular life sciences : CMLS》2010,67(8):1315-1329
Burn injury causes an immunosuppression associated with suppressed adaptive immune function. Dendritic cells (DCs) are APCs
for which signaling via their Toll-like receptors (TLRs) induces their maturation and activation, which is essential for the
adaptive immune response. In this study, we examined if burn injury alters the TLR activity of splenic DCs. After injury,
we noticed that DC functions were impaired, characterized by a suppressed capacity to prime naive T cells when triggering
the TLR4 signaling cascade using specific ligands (LPS or rHSP60). The observed perturbations on LPS-primed DCs isolated from
burned mice exhibited significantly diminished IL-12p40 production and enhanced IL-10 secretion-associated impairment in mitogen-activated
protein kinase activation. Interestingly, we observed a decrease of TLR4/MD-2 expression on the CD8α+ DC subset that persisted following LPS stimulation. The altered TLR4 expression on LPS-stimulated CD8α+ DCs was associated with reduced capacity to produce IL-12 after stimulation. Our results suggested that TLR4 reactivity on
DCs, especially CD8α+ DCs, is disturbed after burn injury. 相似文献
10.
Catherine Aude-Garcia Christian Villiers Serge M. Candéias Catherine Garrel Caroline Bertrand Véronique Collin Patrice N. Marche Evelyne Jouvin-Marche 《Cellular and molecular life sciences : CMLS》2011,68(4):687-696
The cellular prion glycoprotein (PrPC) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate
in vitro and in vivo that PrPC is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione,
we show that PrP−/− thymocytes display a higher susceptibility to H2O2 exposure than PrP+/+ cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level
of ROS, PrP−/− thymocytes are more sensitive to oxidative stress. PrPC function appears to be specific for oxidative stress, since no significant differences are observed between PrP−/− and PrP+/+ mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation
in the thymus. Taken together, our results clearly ascribe to PrPC a protective function in thymocytes against oxidative stress. 相似文献
11.
High frequency of human cytomegalovirus (HCMV)-specific CD8+-T cells detected in a healthy CMV-seropositive donor 总被引:2,自引:0,他引:2
Lang KS Moris A Gouttefangeas C Walter S Teichgräber V Miller M Wernet D Hamprecht K Rammensee HG Stevanovic S 《Cellular and molecular life sciences : CMLS》2002,59(6):1076-1080
Human cytomegalovirus (HCMV) persists after infection but is controlled by cellular immune responses, particularly by CD8+ T cells. If infected individuals are immunosuppressed, HCMV can be reactivated. Upon testing the blood of healthy donors
with human lymphocyte antigen tetramers, we found one individual with about 50 % of his CD8+ T cells being specific for the immunodominant pp65 epitope NLVPMVATV. Over a period of 2 years the high level of HCMV-specific
T cells was maintained, and no HCMV DNA could be detected. At one timepoint, however, HCMV-specific DNA was detected, while
65 % of CD8+ T cells were specific for HCMV. When virus was detectable, a lower percentage of HCMV-specific CD8+ T cells showed interferon γ (IFN-γ) production after peptide stimulation in vitro. These data suggest that HCMV reactivation
may also occur in immunocompetent persons, accompanied by the presence of HCMV-specific CD8+ T cells which are not producing IFNγ, and therefore potentially anergic or in vivo exhausted.
Received 6 March 2002; received after revision 15 April 2002; accepted 17 April 2002 相似文献
12.
Qian Zhang Yunjiang Feng Derek Kennedy 《Cellular and molecular life sciences : CMLS》2017,74(5):777-801
Chemotherapy is one of the most effective and broadly used approaches for cancer management and many modern regimes can eliminate the bulk of the cancer cells. However, recurrence and metastasis still remain a major obstacle leading to the failure of systemic cancer treatments. Therefore, to improve the long-term eradication of cancer, the cellular and molecular pathways that provide targets which play crucial roles in drug resistance should be identified and characterised. Multidrug resistance (MDR) and the existence of tumor-initiating cells, also referred to as cancer stem cells (CSCs), are two major contributors to the failure of chemotherapy. MDR describes cancer cells that become resistant to structurally and functionally unrelated anti-cancer agents. CSCs are a small population of cells within cancer cells with the capacity of self-renewal, tumor metastasis, and cell differentiation. CSCs are also believed to be associated with chemoresistance. Thus, MDR and CSCs are the greatest challenges for cancer chemotherapy. A significant effort has been made to identify agents that specifically target MDR cells and CSCs. Consequently, some agents derived from nature have been developed with a view that they may overcome MDR and/or target CSCs. In this review, natural products-targeting MDR cancer cells and CSCs are summarized and clustered by their targets in different signaling pathways. 相似文献
13.
Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNR+PDGFRα+KDR+ mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβ+CD271+EMCN+DLK1+CD73? primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3–4 days of clonogenic cultures. MB-derived primitive mesenchymal cells have potential to differentiate into mesenchymal stromal/stem cells (MSCs), pericytes, and smooth muscle cells. In this review, we summarize the specification and developmental potential of MBs, emphasize features that distinguish MBs from other mesenchymal progenitors described in the literature and discuss the value of these findings for identifying molecular pathways leading to MSC and vasculogenic cell specification, and developing cellular therapies using MB-derived progeny. 相似文献
14.
In renal carcinoma cells (RCC4) hypoxia inducible factor-1 (HIF-1) is constitutively expressed due to a von Hippel Lindau
protein deficiency, but can be degraded by calpain, independently of the 26S proteasome, when exposed to hypoxia/nitric oxide
(NO). In this study we examined molecular mechanisms to explain calpain activation. The inability of hypoxia/NO to degrade
HIF-1α in respiratory-deficient RCC4-ρ0 cells pointed to the requirement for mitochondria-derived reactive oxygen species.
A prerequisite for O
2
−
in combination with NO to destabilize HIF-1α was corroborated in RCC4-p0 cells, when the redox cycler 2,3-dimethoxy-1,4-naphthoquinone
was used as a source of superoxide. Degradation of HIF-1α required intracellular calcium transients and calpain activation.
Using uric acid to interfere with signal transmission elicited by NO/O
2
−
blocked HIF-1α degradation and attenuated a calcium increase. We conclude that an oxidative signal as a result of NO/O
2
−
coformation triggers a calcium increase that activates calpain to degrade HIF-1α, independently of the proteasome.
Received 14 August 2007; received after revision 4 October 2007; accepted 22 October 2007 相似文献
15.
Lucas Matt Stylianos Michalakis Franz Hofmann Verena Hammelmann Andreas Ludwig Martin Biel Thomas Kleppisch 《Cellular and molecular life sciences : CMLS》2011,68(1):125-137
Neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to modulate spontaneous activity, resting
membrane potential, input resistance, afterpotential, rebound activity, and dendritic integration. To evaluate the role of
HCN2 for hippocampal synaptic plasticity, we recorded long-term potentiation (LTP) in the direct perforant path (PP) to CA1
pyramidal cells. LTP was enhanced in mice carrying a global deletion of the channel (HCN2−/−) but not in a pyramidal neuron-restricted knockout. This precludes an influence of HCN2 located in postsynaptic pyramidal
neurons. Additionally, the selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons
in wild-type but not HCN2−/− mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells. Finally, we found
amplified LTP in the PP of mice carrying an interneuron-specific deletion of HCN2. We conclude that HCN2 channels in inhibitory
interneurons modulate synaptic plasticity in the PP by facilitating the GABAergic output onto pyramidal neurons. 相似文献
16.
Wen Y Fang W Xiang LX Pan RL Shao JZ 《Cellular and molecular life sciences : CMLS》2011,68(15):2615-2626
CD4+CD25+Foxp3+ regulatory T cells (Treg cells) are critical for the maintenance of peripheral tolerance, and the suppression of autoimmune
diseases and even tumors. Although Treg cells are well characterized in humans, little is known regarding their existence
or occurrence in ancient vertebrates. In the present study, we report on the molecular and functional characterization of
a Treg-like subset with the phenotype CD4-2+CD25-like+Foxp3-like+ from a pufferfish (Tetraodon nigroviridis) model. Functional studies showed that depletion of this subset produced an enhanced mixed lymphocyte reaction (MLR) and
nonspecific cytotoxic cell (NCC) activity in vitro, as well as inflammation of the intestine in vivo. The data presented here
will not only enrich the knowledge of fish immunology but will also be beneficial for a better cross-species understanding
of the evolutionary history of the Treg family and Treg-mediated regulatory networks in cellular immunity. 相似文献
17.
R. M. H. Ravindranath M. H. Ravindranath M. C. Graves 《Cellular and molecular life sciences : CMLS》1997,53(9):750-758
IgM antibodies directed against neuronal gangliosides GM1 , GM2 , GD1a , GD1b and GT1b occur in normal individuals and their level significantly decreases with age. Patients with lower motor neuron disease (LMND)
produce high levels of these autoantibodies. AntiGM1 IgM is selectively augmented. In these patients, the CD5+ (B1) and CD5− (B2) subsets of B cells are not distinct entities
but range from those without detectable CD5 marker to those with high CD5+ expression. B1 B cells were sorted to homogeneity,
but B2 B cell cannot be isolated to homogeneity because of the presence of B1 cells with low CD5 expression. In short term
cultures both the subsets produced IgM antibodies, but the antibodies reacted better with desialylated GM1 than with GM1 . Cycloheximide (Cx) (0.35 mM) largely blocked IgM synthesis of the B1 B cells but inhibition of the B2 B cells was incomplete,
possibly due to shedding of cytophilic antibodies as well as to the presence of B1 phenotype with loss of CD5 expression.
CD5+ B cells may be involved in the production of antiglycolipid IgM.
Received 9 June 1997; received after revision 21 July 1997; accepted 28 July 1997 相似文献
18.
Liao HF Yang YC Chen YY Hsu ML Shieh HR Chen YJ 《Cellular and molecular life sciences : CMLS》2007,64(1):104-111
Dendritic cells (DC) are specialized antigen-presenting cells. Bone marrow monocytes have been widely used to generate murine
myeloid DC. We found that mouse macrophages derived from bone marrow CD11b+ monocytes influenced the differentiation of these precursors into DC. Modulation of differentiation was demonstrated by the
down-regulation of CD11c, CD40, and CD86 expression and by IL-12 production. DC differentiated in the presence of conditioned
medium from bone marrow-derived macrophage culture (MCM) had impaired ability to stimulate proliferation of, and IFN- γ production
by, allogeneic CD4+ T cells. This inhibition of DC differentiation was mainly mediated by secretory products from macrophages but not by cell-cell
contact. MCM contained higher concentrations of macrophage-colony-stimulating factor (M-CSF), IL-10, and TGF- β1, whereas
IL-6 remained unchanged compared with conditioned medium from fresh monocytes. M-CSF may be the major mediator in MCM inhibiting
DC differentiation. This study demonstrates an important influence of bone marrow-derived macrophages on DC precursors during
DC differentiation.
Received 12 September 2006; received after revision 20 October 2006; accepted 13 November 2006 相似文献
19.
目的研究胃癌侧群(Side Population,sP)细胞对化疗药物5-Fu(氟尿嘧啶)的耐药性及可能机制,并检测干细胞相关基因Nanog、Musashi-1及cD44的表达情况。方法选择人胃癌细胞株sGc-7901,以荧光染料H0echst 33342染色,维拉帕米桔抗对照,应用流式细胞仪分选sP细胞和nonsP细胞。细胞耐药实验比较sP细胞与nonsP细胞对化疗药物5.Fu的耐药性差异;westem_h10t检测ABcG2和bcl-2蛋白表达情况;流式细胞仪分析细胞周期;荧光定量PcR检测两组细胞中干细胞相关基因Nanog、Musashi-1及cD44mRNA的表达差异。结果胃癌细胞株sGc.790l中sP细胞的比例为2.8%,sP细胞对5-Fu的耐药存活率明显高于non-sP细胞(P〈0.05),与nonsP细胞相比,sP细胞高表达耐药蛋白ABcG2和抗凋亡蛋白bcl-2,有更多的细胞处于c0/G1期(P〈0.05),并高表达干细胞相关基因Musashi-1和cD44。结论胃癌sGC_7901细胞株中sP细胞对化疗药物5.Fu的耐药性明显高于nonsP细胞,其耐药机制可能与sP细胞高表达耐药蛋白ABcG2和抗凋亡蛋白bcl-2,有更多细胞处于G0/Gl期有关;Musashi-1和cD44可能是相对特异性的胃癌干细胞标志物。 相似文献
20.
Fu WX Gong SY Qian XP Li Y Zhu ML Dong XY Li Y Chen WF 《Cellular and molecular life sciences : CMLS》2004,61(15):1935-1945
Mouse platelet basic protein (CXCL7/mPBP) was cloned from thymic stromal cells and further identification
indicated that it was expressed in thymic monocytes/macrophages (Mo/Ms). Recombinant mPBP was
chemoattractive for target cells of polymorphonuclear leucocytes, peritoneal Mo/Ms and splenic lymphocytes
with distinct potencies. CXCR2 was identified to be a cognate receptor for mPBP. Mouse thymocyte subsets of
CD4-CD8- double-negative (DN),
CD4+CD8+ double-positive (DP),
CD4+CD8- single-positive (CD4SP)
and CD4-CD8+ single-positive (CD8SP) expressed cell surface
CXCR2 with different positive percentages and expression levels. mPBP was chemoattractive for thymocyte subsets
with the potency order DN>DP> CD8SP>CD4SP, consistent with the levels of CXCR2 expressed on the
respective cells. Thus, mPBP in thymus is functionally redundant with chemokine CXCL12/ SDF-1. Moreover, our
finding that thymic Mo/Ms can produce mPBP implies that they may have other functions apart from acting as
scavengers in thymus.Received 25 March 2004; received after revision 10 May 2004; accepted 8 June 2004 相似文献