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1.
Mammalian interleukin-4 (IL-4) and IL-13 are T helper type 2 (Th2) cytokines with pleiotropic functions in immunity. They
signal through receptors containing IL-4Rα and IL-2Rγ or IL-13Rα1. In addition, a decoy receptor, IL-13Rα2, is known to exist
and modulates the function of IL-13. The existence of fish orthologues to mammalian IL-4 and IL-13 is still under debate.
However, the receptor chains have been predicted in zebrafish, and we have previously cloned IL-2Rγ and IL-13Rα2 in rainbow
trout. In this study, we have cloned a further five novel trout IL-4/13 receptors. Thus, each of the IL-4Rα, IL-13Rα1 and
IL-13Rα2 chains has two copies. The identities of the receptors is supported by homology analysis, characteristic domain structure,
phylogenetic tree analysis and synteny analysis in zebrafish. However, the characteristic WSXWS motif of structural importance
in mammalian type I cytokine receptors is missing in all fish IL-4Rα and IL-13Rα1 molecules. All the receptors have a characteristic
domain structure that is similar to their mammalian counterparts except for IL-13Rα1b that has the N-terminal Ig domain missing.
Since this Ig domain is a specific and critical binding unit for IL-13 but not for IL-4 signalling, its absence potentially
converts the IL-13Rα1b into a receptor that can only signal via IL-4 ligation. The existence of duplicated receptor genes
perhaps suggests that more ligands still remain to be discovered that will bind these receptors. The duplicated receptors
are differentially expressed in most tissues and cell lines examined, and their expression can be modulated by LPS, polyIC
and IFN-γ in cell lines. In contrast, the T-cell stimulant phytohaemagglutinin increased the expression of IL-4Rα1 and IL-4Rα2,
but not IL-13Rα1/2, suggesting a role of an IL-4-like molecule in T-cell growth/activation in fish. 相似文献
2.
3.
Tomohiro Yamaguchi Youichi Suzuki Ryuichi Katakura Takusaburo Ebina Junkichi Yokoyama Yoshiaki Fujimiya 《Cancer immunology, immunotherapy : CII》1998,47(2):97-103
γδT cells play a regulatory role in both primary and metastatic tumor growth in humans. The mechanisms responsible for the
activation and proliferation of circulating γδT cells should be fully understood prior to their adoptive transfer to cancer
patients. We have examined in vitro functional effects of interleukin-15 (IL-15) on highly purified γδT cells isolated from
glioblastoma patients. γδT cells constitutively express the heterotrimeric IL-2 receptor (IL-2R) αβγ, but the levels of IL-2Rβ
or γ expression were not increased by incubation with saturating amounts of IL-15. IL-15 was shown to induce a maximal γδT
cell proliferation, although at much higher concentrations (at least 2000 U/ml) than IL-2 (100 U/ml). Submaximal concentrations
of IL-15 plus low concentrations of IL-2 produced an additive proliferative response. In contrast to the IL-2-induced response,
this activity was completely or partially abrogated by anti-IL-2Rβ, or anti-IL-2Rγ antibodies, but not by anti-IL-2Rα antibodies.
Incubation of γδT cells in the presence of IL-15 resulted not only in the appearance of NK and LAK activity, but also in specific
autologous tumor cell killing activity, an additive effect being seen with IL-15 and IL-2. This IL-15-induced tumor-specific
activity could be significantly blocked by anti-IL-2Rγ and anti-IL-2R-β mAb, but not by anti-IL-2Rα mAb. Thus, in contrast
to IL-2, IL-15 activates tumor-specific γδT cells through the components of IL-2Rβ and IL-2Rγ, but not IL-2Rα. These enhanced
in vitro tumor-specific and proliferative responses of γδT cells seen with IL-15 suggest a rational adjuvant imunotherapeutic
use of γδT cells in cancer patients.
Received: 23 January 1998 / Accepted: 20 May 1998 相似文献
4.
Fischer U Keller A Leidinger P Deutscher S Heisel S Urbschat S Lenhof HP Meese E 《Molecular cancer research : MCR》2008,6(4):576-584
To further understand the biological significance of amplifications for glioma development and recurrencies, we characterized amplicon frequency and size in low-grade glioma and amplicon stability in vivo in recurring glioblastoma. We developed a 12q13-21 amplicon-specific genomic microarray and a bioinformatics amplification prediction tool to analyze amplicon frequency, size, and maintenance in 40 glioma samples including 16 glioblastoma, 10 anaplastic astrocytoma, 7 astrocytoma WHO grade 2, and 7 pilocytic astrocytoma. Whereas previous studies reported two amplified subregions, we found a more complex situation with many amplified subregions. Analyzing 40 glioma, we found that all analyzed glioblastoma and the majority of pilocytic astrocytoma, grade 2 astrocytoma, and anaplastic astrocytoma showed at least one amplified subregion, indicating a much higher amplification frequency than previously suggested. Amplifications in low-grade glioma were smaller in size and displayed clearly different distribution patterns than amplifications in glioblastoma. One glioblastoma and its recurrencies revealed an amplified subregion of 5 Mb that was stable for 6 years. Expression analysis of the amplified region revealed 10 overexpressed genes (i.e., KUB3, CTDSP2, CDK4, OS-9, DCTN2, RAB3IP, FRS2, GAS41, MDM2, and RAP1B) that were consistently overexpressed in all cases that carried this amplification. Our data indicate that amplifications on 12q13-21 (a) are more frequent than previously thought and present in low-grade tumors and (b) are maintained as extended regions over long periods of time. 相似文献
5.
Newborn calves lack a mature immune system. The immune system develops with age, but the role of the expression of cytokine
receptors in the development of immune cells of Peyer’s patches (PPs) in the intestines of calves in the first 2 months has
not yet been elucidated. In this study, the distribution of immune cells and the expression of interleukin (IL) receptors
(R) in the ileal PPs of newborn and 2-month-old calves were investigated immunohistochemically with monoclonal antibodies
against bovine CD4, CD8, IgM, γδTCR, T19, WC3, WC5, and WC6 antigens. The expression of ILRs was examined with antibodies
against CD25 (IL-2Rα), IL-2Rγ, IL-4R, IL-6R, IL-10R, and IL-13R antigens. CD4+, CD8+, γδTCR+, T19+, and WC6+ cells were found to be more widely distributed in the ileal PPs of 2-month-old calves than in those of newborn calves. Moreover,
the expression of CD25 (IL-2Rα), IL-4R, and IL-13R in the ileal PPs of 2-month-old calves was more prominent than that in
newborn calves. These data suggest that the immune system of calves at 2 months of age is developed by reactions to foreign
antigens and aging. 相似文献
6.
Background
Although IL-4 and IL-13 share the IL-13 receptor, IL-13 exhibits unique functions. To elicit the cellular basis of these differences, signal transduction processes have been compared. Additionally, the role of the IL-4 receptor alpha (IL-4Rα) variant Q551R was investigated. 相似文献7.
Astrocytomas represent the most common form of glial tumors. The most malignant grade of these tumors, glioblastoma multiforme, may arise as a malignant progression from low-grade astrocytoma through anaplastic astrocytoma to secondary GBM, or else it may arise "de novo" as primary GBM. Both types of glioblastoma are usually histologically indistinguishable. However, distinct molecular alterations have been described between them that potentially allow differentiation between the two mechanisms of origin. Since malignant transformation is a multistep process, we summarize in this review the earliest genetic changes that seem to be involved in the appearance and development of low-grade astrocytic tumors, where early detection and treatment could be possible. 相似文献
8.
Expression of the neurotrophin receptors Trk A and Trk B in adult human astrocytoma and glioblastoma 总被引:4,自引:0,他引:4
Wadhwa S Nag TC Jindal A Kushwaha R Mahapatra AK Sarkar C 《Journal of biosciences》2003,28(2):181-188
Neurotrophins and their receptors of the Trk family play a critical role in proliferation, differentiation and survival of
the developing neurons. There are reports on their expression in neoplasms too, namely, the primitive neuroectodermal tumours
of childhood, and in adult astrocytic gliomas. The involvement of Trk receptors in tumour pathogenesis, if any, is not known.
With this end in view, the present study has examined 10 tumour biopsy samples (identified as astrocytoma, pilocytic astrocytoma
and glioblastoma) and peritumoral brain tissue of adult patients, for the presence of Trk A and Trk B receptors, by immunohistochemistry.
The nature of the tumour samples was also confirmed by their immunoreactivity (IR) to glial fibrillary acidic protein. In
the peritumoral brain tissue, only neurons showed IR for Trk A and Trk B. On the contrary, in the tumour sections, the IR
to both receptors was localized in the vast majority of glia and capillary endothelium. There was an obvious pattern of IR
in these gliomas: high levels of IR were present in the low-grade (type I and II) astrocytoma; whereas in the advanced malignant
forms (WHO grade IV giant cell glioblastoma and glio-blastoma multiforme) the IR was very weak. These findings suggest that
Trk A and Trk B are involved in tumour pathogenesis, especially in the early stage, and may respond to signals that elicit
glial proliferation, and thus contribute to progression towards malignancy. 相似文献
9.
Michael Kraich Markus Klein Edwin Patiño Henning Harrer Joachim Nickel Walter Sebald Thomas D Mueller 《BMC biology》2006,4(1):13-18
Background
Interleukin 4 (IL-4) is a key regulator of the immune system and an important factor in the development of allergic hypersensitivity. Together with interleukin 13 (IL-13), IL-4 plays an important role in exacerbating allergic and asthmatic symptoms. For signal transduction, both cytokines can utilise the same receptor, consisting of the IL-4Rα and the IL-13Rα1 chain, offering an explanation for their overlapping biological functions. Since both cytokine ligands share only moderate similarity on the amino acid sequence level, molecular recognition of the ligands by both receptor subunits is of great interest. IL-4 and IL-13 are interesting targets for allergy and asthma therapies. Knowledge of the binding mechanism will be important for the generation of either IL-4 or IL-13 specific drugs. 相似文献10.
Interleukin (IL)-6, the founding member of IL-6 family cytokines, plays non-redundant roles in hematopoiesis and acute phase
responses. IL-6 signals via a specific private IL-6Rα and a common beta chain gp130. In this study, we have cloned both the
IL-6Rα and gp130 in rainbow trout. The trout gp130 cDNA encodes 906 aa and is similar in size, extracellular domain structure
(D1–D6) and presence of intracellular motifs important for signal transduction to tetrapod gp130s. The trout IL-6Rα cDNA encodes
for 834 aa and is larger compared to tetrapod IL-6Rαs, as are other fish IL-6Rα molecules due to a large D1 domain. However,
the cytokine-binding domain is well conserved across vertebrates, with four conserved cysteine residues in the N-terminal
FNIII domain and a WSXWS motif in the C-terminal FNIII domain. Furthermore, a phylogenetic tree analysis confirmed that the
reported fish IL-6Rα and gp130 molecules are orthologues to their tetrapod counterparts. The extra large D1 domain of the
salmonid IL-6Rα molecules results partially from the insertions of two repetitive sequences of [TS]-[TF]-VSTTT-[ND]-TTSNG
and TTVS-[AT]-IKD-[DG]-S-[KD]-N-[GR], respectively. Furthermore the numbers of repetitions of the two motifs were variable
in different individuals and cell lines, and even in the same fish allelic polymorphism exists. Trout IL-6Rα was expressed
at higher levels than gp130 in a number of tissues examined and the expression of both IL-6Rα and gp130 could be modulated
by LPS and Poly I:C in the cell lines studied. The expression patterns of the receptors suggest that high level expression
of IL-6Rα is critical for IL-6 responsiveness. 相似文献
11.
Cao S Liu Z Guo A Li Y Zhang C Gaobing W Chunfang F Tan Y Chen H 《Protein expression and purification》2008,60(1):25-30
The receptor binding to interleukin (IL)-13 is composed of the IL-13 receptor α1 chain (IL-13Rα1) and the IL-4 receptor α chain (IL-4Rα). In order to investigate the interaction of IL-13 with IL-13Rα1 and IL-4Rα, the DNA fragments coding the extracellular regions of human IL-13Rα1 and the IL-4Rα (containing a cytokine receptor homologous region) were fused with mouse Fc and expressed by a silkworm–baculovirus system. The expressed receptors were successfully purified by affinity chromatography using protein A, and the Fc region was removed by thrombin digestion. After further purification with anion-exchange chromatography, these receptors were used to investigate the ligand–receptor interaction. Size exclusion chromatography and SPR analysis revealed that mixture of IL-13 and IL-13Rα1 showed predominant affinity to IL-4Rα, although neither detectable affinity of IL-13 nor IL-13Rα1 was observed against IL-4Rα. Combining these data with the moderate affinity of IL-13 to IL-13Rα1, this indicates that IL-13 first binds to IL-13Rα1 and recruits consequently to IL-4R. 相似文献
12.
Interleukin-7 receptor α chain (IL-7Rα)-derived signals are critical for normal T cell development, mature T cell homeostasis,
and longevity of memory T cells. IL-7Rα expression in T cells is dynamically regulated at different developmental and antigen-responding
stages. However, the molecular mechanism underlying the dynamic regulation is not completely understood. Here we describe
generation of a bacterial artificial chromosome (BAC)-based reporter transgenic mouse strain, which contains 210 kb DNA sequence
flanking the Il7r locus. We used in vitro validated EGFP reporter and insulator sequences to facilitate the reporter transgene expression.
Consistent with endogenous IL-7Rα expression, the BAC transgene was expressed in mature T cells, a portion of natural killer
cells but not in mature B cells. In the thymus, the EGFP reporter and endogenous IL-7Rα showed synchronized silencing in CD4+CD8+ double positive stage, were both upregulated in CD4+ or CD8+ single positive thymocytes, and both continued to be co-expressed in na?ve T cells in the periphery. Upon encountering antigen,
the antigen-specific effector CD8+ T cells downregulated both endogenous IL-7Rα and the EGFP reporter, which were upregulated in synchrony in antigen-specific
memory CD8 T cells. These results indicate that the BAC-EGFP transgene reports endogenous IL-7Rα regulation with high fidelity,
and further suggest that the 210 kb sequence flanking the Il7r locus contains sufficient genetic information to regulate its expression changes in T lineage cells. Our approach thus represents
a critical initial step towards systematic dissection of the cis regulatory elements controlling dynamic IL-7Rα regulation during T cell development and cellular immune responses. 相似文献
13.
Ursula Elsässer-Beile Ulrich Wetterauer Wolfgang Schultze-Seemann Harald Gallati Jürgen Schulte Mönting Sabine von Kleist 《Cancer immunology, immunotherapy : CII》1996,42(2):93-98
The immunological properties of tumor-infiltrating (TIL) and peripheral blood lymphocytes (PBL) from 29 patients with renal
cell carcinomas were characterized with respect to their phenotypic expression and cytokine production. TIL were isolated
from mechanically disaggregated tumor material and PBL from peripheral blood by gradient centrifugation. To eliminate all
non-lymphoid cells, CD3-positive cells were specifically separated from these cell fractions with anti-CD3 magnetic beads.
These pure CD3-positive PBL (CD3+PBL) and TIL (CD3+TIL) were cultured with pokeweed mitogen and the levels of the cytokines interleukin-1α (IL-1α), IL-1β, IL-2, interferon γ
(IFNγ), and tumor necrosis factor α (TNFα) measured in the 4-day post-inductional cell culture supernatants. In all cell cultures
a wide range of cytokine values was found, indicating a large variation in the immunological activity of the lymphocytes of
each individual. When the cell cultures of the CD3+TIL and CD3+PBL were compared in each patient similar values for IL-1α, IL-1β, IFNγ and TNFα were found. However CD3+TIL produced significantly lower levels of IL-2 than CD3+PBL upon mitogenic stimulation. This may be due to a lower CD4/CD8 ratio in the CD3+TIL as compared to the CD3+PBL. These results suggest that there are no fundamental qualitative and quantitative differences in the lymphokine-producing
capacity of CD3+TIL and CD3+PBL derived from patients with renal cell carcinomas.
Received: 8 August 1995 / Accepted: 23 January 1996 相似文献
14.
Treatment of recurrent glioma with intracavitary alloreactive cytotoxic T lymphocytes and interleukin-2 总被引:4,自引:0,他引:4
C. A. Kruse Linda Cepeda Betty Owens Stephen D. Johnson John Stears Kevin O. Lillehei 《Cancer immunology, immunotherapy : CII》1997,45(2):77-87
For a single-dose toxicity assessment, five patients with recurrent malignant glioma (ages 29–46 years) were treated with
intracavitary alloreactive cytotoxic T lymphocytes (CTL) and interleukin-2 (IL-2). The trial tested the hypothesis that alloreactive
CTL, sensitized to the major histocompatibility complex (MHC) proteins of the patient, offer selective, targeted killing of
glioma cells that express MHC. Patient lymphocytes, which also express MHC, were irradiated and placed into CellMax artificial
capillary systems with lymphocytes from MHC-disparate donors and CTL developed over a 2- to 3-week period with a low concentration
of IL-2. The CTL largely expressed CD3 and CD11a/CD8 markers and lysed targets displaying patient MHC. CTL were implanted
into the tumor bed at surgery and a catheter was used for subsequent infusions. Patients received one to five treatment cycles
every other month; one cycle generally consisted of two or three CTL infusates administered within a 1- to 2-week period.
Different unrelated donors were used for each cycle. Treatment was well tolerated; transient toxicity at grades 1–3 was recorded
by NCI Common Toxicity Scale criteria. Two glioblastoma patients have died; one from tumor recurrence locally and the other
from recurrence at a site distant from the treatment. Two of the five patients completed five cycles; one anaplastic oligodendroglioma
patient shows no evidence of tumor 30 months from the start of immune therapy and an anaplastic astrocytoma patient shows
stable disease 28 months after initiation of therapy. One anaplastic oligodendroglioma patient, who dropped the protocol during
her second treatment cycle, has no evidence of tumor 28 months after recurrence.
Received: 21 May 1997 / Accepted: 17 July 1997 相似文献
15.
Janice J. Jensen Ursula H. Winzer-Serhan Frances M. Leslie 《Journal of neurochemistry》1997,68(1):112-120
Abstract: Primary embryonic cortical cultures were used as an in vitro model to evaluate the influence of glia on developmental expression of α7-type nicotinic acetylcholine receptors in rat brain. In cells cultured in serum-containing medium without mitotic inhibitors, specific 125 I-α-bungarotoxin binding to α7-type nicotinic receptors was maximal 4–8 days after plating. Treatment with 5'-fluorodeoxyuridine (80 µ M ) from 1 to 3 days in vitro significantly reduced glial proliferation and concomitantly increased 125 I-α-bungarotoxin binding, whereas plating onto a glial bed layer decreased binding. There was no significant binding to pure glial cultures. Treatment-induced changes in neuronal binding resulted from alterations in receptor density, with no change in affinity. 5'-Fluorodeoxyuridine treatment also increased cellular expression of α7 receptor mRNA but had no effect on N -[3 H]methylscopolamine binding to muscarinic receptors. Glial conditioned medium decreased 125 I-α-bungarotoxin binding in both control and 5'-fluorodeoxyuridine-treated cultures, suggesting the release of a soluble factor that inhibits α7-type nicotinic receptor expression. An additional mechanism of glial regulation may involve removal of glutamate from the surrounding medium, as added glutamate (200 µ M ) increased 125 I-α-bungarotoxin binding in astrocyte-poor cultures but not in those that were astrocyte enriched. These results suggest that glia may serve a physiological role in regulating α7-type nicotinic receptors in developing brain. 相似文献
16.
Hall IP 《Respiratory research》2000,1(1):6-8
The interleukin-4 (IL-4) signalling cascade has been identified as a pathway potentially important in the development of asthma.
Genetic variants within this signalling pathway might contribute to the risk of developing asthma in a given individual. A
number of polymorphisms have been described within the IL-4 receptor α (IL-4Rα) gene. In addition polymorphism occurs in the
promoter for the IL-4 gene itself. This commentary accompanies a paper by C Oberet al describing the contribution of IL-4Rα polymorphism to susceptibility to asthma and atopy in the Hutterite population and
other outbred populations collected during the collaborative studies on the genetics of asthma (CSGA) programme. 相似文献
17.
To clarify the response of leptomeningeal cells to immune stimulation, the effect of lipopolysaccharide (LPS) on expression
of IL-6 receptors in the cultured leptomeningeal cells was investigated. The results showed that the expression of IL-6Rα
was invisible in the purified leptomeningeal cells while it was seen in the cells when they were co-cultured with astrocytes.
On the other hand, GP130 was moderately expressed in both conditions. Following incubation with different doses of LPS, IL-6Rα
expression in purified leptomeningeal cells was increased in a time- and dose-dependent manner, while GP130 level remained
unchanged. Concomitantly, phosphorylated ERK1/2 level was increased following LPS stimulation and its inhibition by PD98059
attenuated the LPS-induced increase of IL-6Rα expression. These data indicate that leptomeningeal cells can respond to immunogenic
stimuli as manifested by expression of cytokine receptors. Moreover, ERK1/2 pathway seems to be involved in the process of
LPS-induced IL-6Rα up-regulation in leptomeningeal cells. 相似文献
18.
Koichi Iwasaki Steven A. Toms Gene H. Barnett Melinda L. Estes Manjula K. Gupta Barbara P. Barna 《Cancer immunology, immunotherapy : CII》1995,40(4):228-234
We reported previously that tumor necrosis factor α (TNFα) inhibited proliferation and invasiveness of human malignant glial cells. Because tamoxifen, an estrogen antagonist, has also been shown to inhibit growth of such cells, we hypothesized that a combination of tamoxifen and TNFα might be more effective than either reagent alone. TNFα (1–100 ng/ml) or tamoxifen (80 ng/ml-2 μg/ml) alone inhibited proliferation of a human glioblastoma cell line (WITG3) in a dose-dependent fashion; in combination, tamoxifen and TNFα yielded additive growth inhibition. Apoptotic cells characterized by nuclear fragmentation were detectable after 48 h of TNFα or tamoxifen exposure and were significantly increased by combination treatment. In non-neoplastic human astroglia and fibroblasts, proliferation was unaffected by tamoxifen, and enhanced by TNFα as previously reported. Staurosporine (2–50 nM), which has been reported to augment the effects of TNFα, was less effective than tamoxifen against WITG3 and, in addition, was markedly inhibitory to non-neoplastic glial cells. Binding studies yielded no evidence of WITG3 estrogen or progesterone receptors, nor of tamoxifen effects on TNFα receptors. Data suggest that TNFα and tamoxifen in combination display growth-regulatory properties, which (a) are more inhibitory to human glioblastoma cells than either agent alone, (b) do not affect non-neoplastic glia, (c) do not require either estrogen/ progesterone receptors or alteration of external TNFα receptors, and (d) may involve apoptosis. 相似文献
19.
Nie H Li Z Lukas RJ Shen Y Song L Wang X Yin M 《Cellular and molecular neurobiology》2008,28(1):103-112
(1) Nicotinic acetylcholine receptors in central nervous system are thought to be new targets for Alzheimer’s disease. However,
the most involved nicotinic receptor subtype in Alzheimer’s disease is unclear. α4β2 receptor is the most widely spread subtype
in brain, involving in several important aspects of cognitive and other functions. We constructed cell line by transfecting
human amyloid precursor protein (695) gene into SH-EP1 cells which have been transfected with human nicotinic receptor α4
subunit and β2 subunit gene, to observe effects of α4β2 receptors activation on β-amyloid, expecting to provide a new cell
line for drug screening and research purpose. (2) Liposome transfection was used to express human amyloid precursor protein
(695) gene in SH-EP1-α4β2 cells. Function of the transfected α4β2 receptors was tested by patch clamp. Effects of nicotine
and epibatidine (selective α4β2 nicotinic receptor agonist) on β-amyloid were detected by Western blot and ELISA. Effects
of nicotine and epibatidine on amyloid precursor protein (695) mRNA level were measured using real-time PCR. (3) Human amyloid
precursor protein (695) gene was stably expressed in SH-EP1-α4β2 cells; Nicotine (1 μM) and epibatidine (0.1 μM) decreased
intracellular and secreted β-amyloid in the cells; and activation of α4β2 receptors did not affect amyloid precursor protein
(695) mRNA level. (4) These results suggest that the constructed cell line, expressing both amyloid precursor protein (695)
gene and human nicotinic receptor α4 subunit and β2 subunit gene, might be useful for screening specific nicotinic receptor
agonists against Alzheimer’s disease. Alteration of Aβ level induced by activation of α4β2 nAChR in our study might occur
at a post-translational level. 相似文献
20.
Qiu B Zhang D Wang C Tao J Tie X Qiao Y Xu K Wang Y Wu A 《Molecular biology reports》2011,38(5):3585-3591
Immune-associated cytokines including IL-10 and TGF-β2 are thought to play a crucial role in immunosuppression mediated by
gliomas. We have investigated the possibility that glioma stem cells are the major source of these cytokines. Tumor spheres,
clonal non-adherent cell colonies derived from a single tumor stem cell, were cultured from surgical specimens of eight glioma
patients, including two glioblastoma multiformes (grade IV), one anaplastic oligodendroglioma (grade III) and five anaplastic
astrocytomas (grade III). Real-time RT-PCR and immunoassay were used to compare the relative expression levels of IL-10 and
TGF-β2 in stem-cell-derived tumor sphere cells (TSCs) and primary cultured glioma cells (PCGCs). TSCs were confirmed to express
the brain tumor stem cell marker CD133, and on in vitro differentiation gave rise to cells expressing neuronal or glial markers.
RT-PCR and immunoassay revealed that mRNA and protein levels of both IL-10 and TGF-β2 were significantly higher in TSCs than
in PCGCs from the same tumor. Interestingly, the degree of overexpression in TSCs, but not in PCGS, appeared to correlate
with the pathological grade of the glioma. These findings suggest that glioma stem cells are likely to be the major tumor
source of immunosuppressive cytokines and thereby play a crucial role in determining glioma malignancy. 相似文献