Abstract:
:Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites to promote tumor growth, but the underlying mechanisms remain largely elusive. Here, we found that interferon alpha (IFNα)-secreting MSCs showed more dramatic inhibition effect on tumor progression than that of IFNα alone. Interestingly, IFNα-primed MSCs could also effectively suppress tumor growth. Mechanistically, we demonstrated that both IFNα and IFNβ (type I IFNs) reversed the immunosuppressive effect of MSCs on splenocyte proliferation. This effect of type I IFNs was exerted through inhibiting inducible NO synthase (iNOS) expression in IFNγ and TNFα-stimulated MSCs. Notably, only NO production was inhibited by IFNα; production of other cytokines or chemokines tested was not suppressed. Furthermore, IFNα promoted the switch from signal transducer and activator of transcription 1 (Stat1) homodimers to Stat1-Stat2 heterodimers. Studies using the luciferase reporter system and chromatin immunoprecipitation assay revealed that IFNα suppressed iNOS transcription through inhibiting the binding of Stat1 to iNOS promoter. Therefore, the synergistic anti-tumor effects of type I IFNs and MSCs were achieved by inhibiting NO production. This study provides essential information for understanding the mechanisms of MSC-mediated immunosuppression and for the development of better clinical strategies using IFNs and MSCs for cancer immunotherapy.
journal_name
Oncogenejournal_title
Oncogeneauthors
Shou P,Chen Q,Jiang J,Xu C,Zhang J,Zheng C,Jiang M,Velletri T,Cao W,Huang Y,Yang Q,Han X,Zhang L,Wei L,Rabson AB,Chin YE,Wang Y,Shi Ydoi
10.1038/onc.2016.128subject
Has Abstractpub_date
2016-11-17 00:00:00pages
5953-5962issue
46eissn
0950-9232issn
1476-5594pii
onc2016128journal_volume
35pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Neogenin is a member of the N-CAM family of cell adhesion molecules and is closely related to the DCC tumor suppressor gene product. Recently, it has been demonstrated that the DCC/Neogenin subfamily plays a key role in axonal guidance within the embryonic nervous system, however little is known about the function of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201225
更新日期:1997-08-07 00:00:00
abstract::ETS is a family of transcription factors that contain a highly conserved ETS DNA binding domain. Various members of the ETS family are expressed in cells of hematopoietic lineage. ETS-1, ETS-2 and ERGB/FLI-1 are expressed at high levels in T-lymphocytes. HIV-1 infects T-cells and it has been shown that its LTR contain...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-01-04 00:00:00
abstract::CD44 is a cell surface receptor for hyaluronate, a component of the extracellular matrix (ECM). Although CD44 has been implicated in tumor invasion and metastasis, the molecular mechanisms remain to be elucidated. Here we find that CD44 expressed in cancer cells is cleaved at the membrane-proximal region of the ectodo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202447
更新日期:1999-02-18 00:00:00
abstract::SHP-2 protein tyrosine phosphatase plays an important role in activation of the RAS-dependent signaling. Gain-of-function mutations in the PTPN11 gene, which encodes SHP-2, have been found in the leukemia-prone developmental disorder Noonan syndrome as well as sporadic childhood leukemias, indicating that SHP-2 is a b...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1211019
更新日期:2008-06-05 00:00:00
abstract::Both chemokine receptors (CXCRs) 7 and 4 can facilitate immune cell migration and mediate a vast array of physiological and pathological events. Herein we report, in both human and animal studies, that these two CXCRs can form heterodimers in vivo and promote colorectal tumorigenesis through histone demethylation. Com...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0519-2
更新日期:2019-02-01 00:00:00
abstract::The degree of DNA methylation in the c-fos gene and its vicinity in liver, brain and spleen of mice of different ages was examined using methylation-sensitive restriction endonucleases. The gene had an invariable unmethylated domain from 1.8kb upstream of the cap site to the first intron. The domain was flanked on bot...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract::Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and f...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.174
更新日期:2011-11-10 00:00:00
abstract::Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accum...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.519
更新日期:2017-06-29 00:00:00
abstract::To elucidate the mechanisms behind the high sensitivity of myxoid/round cell liposarcoma (MRCL) to trabectedin and the suggested selectivity for specific subtypes, we have developed and characterized three MRCL xenografts, namely ML017, ML015 and ML004 differing for the break point of the fusion gene FUS-CHOP, respect...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.462
更新日期:2014-10-30 00:00:00
abstract::Tumor metastasis is the leading cause of death among breast cancer patients. PELP1 (proline, glutamic acid and leucine rich protein 1) is a nuclear receptor coregulator that is upregulated during breast cancer progression to metastasis and is an independent prognostic predictor of shorter survival of breast cancer pat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.332
更新日期:2014-07-10 00:00:00
abstract::Centromeric instability is characterized by dynamic formation of centromeric breaks, deletions, isochromosomes and translocations, which are commonly observed in cancer. So far, however, the mechanisms of centromeric instability in cancer cells are still poorly understood. In this study, we tested the hypothesis that ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.508
更新日期:2011-03-17 00:00:00
abstract::The intrinsic mitochondrial apoptotic pathway acts through two core pro-apoptotic proteins Bax (Bcl2-associated X protein) and Bak (Bcl2-antagonist/killer 1). Although Bax and Bak seem to have redundant roles in apoptosis, accumulating evidence also suggests that they might not be interchangeable under certain conditi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.497
更新日期:2012-06-28 00:00:00
abstract::All-trans retinoic acid (RA), the principle biologically active form of vitamin A, is essential for many developmental process as well as homeostasis in the adult. Many lines of evidence also suggest that RA, acting through the RA receptors (RARs), can also suppress growth of tumors of diverse origin. To assess direct...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207682
更新日期:2004-07-08 00:00:00
abstract::Aberrant activation of anaplastic lymphoma kinase (ALK) can cause sporadic and familial neuroblastoma. Using a proteomics approach, we identified Bruton's tyrosine kinase (BTK) as a novel ALK interaction partner, and the physical interaction was confirmed by co-immunoprecipitation. BTK is expressed in neuroblastoma ce...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0397-7
更新日期:2018-11-01 00:00:00
abstract::Promyelocytic leukemia (PML) nuclear bodies (PML NBs) are discrete subnuclear domains organized by the promyelocytic leukemia protein PML, a tumor suppressor essential for multiple apoptotic pathways. We have recently described a novel family of cellular factors, the THAP proteins, characterized by the presence at the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206271
更新日期:2003-04-24 00:00:00
abstract::Nerve growth factor induces differentiation and survival of rat PC12 pheochromocytoma cells. The activation of the erk cascade has been implicated in transducing the multitude of signals induced by NGF. In order to explore the role of this signaling cascade in NGF mediated survival, differentiation and proliferation, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202524
更新日期:1999-03-25 00:00:00
abstract::A protein of 300 kDa (p300) associates with the adenovirus E1A proteins and has been implicated in the control of cell cycle progression. In mammalian cells, p300 is actively phosphorylated in both quiescent and proliferating cells and its level of phosphorylation increases as it travels from late G1 into M phase. E1A...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::We have previously reported the isolation of several temperature-sensitive (ts) mutants of F9 cells. Further investigations showed that some mutants were induced to differentiate at non-permissive temperature of cell growth, accompanied by changes in the expression of various genes, whereas others were not. During the...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::The carboxyl terminus of c-Myb contains a negative regulatory domain that is absent in the v-Myb oncoprotein, but conserved among all the known Myb proteins of animals. This domain inhibits transcriptional activation by c-Myb in animal cells, but not in budding yeast, suggesting that additional protein(s) present in a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204048
更新日期:2001-01-04 00:00:00
abstract::The expression of the NH2 terminally truncated ErbB2 receptor (p95ErbB2) in breast cancer correlates with metastatic disease progression compared with the expression of full-length p185ErbB2. We now show that heregulin (HRG), but not EGF, stimulates p95ErbB2 phosphorylation in BT474 breast cancer cells. Furthermore, p...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207166
更新日期:2004-01-22 00:00:00
abstract::Oncogenesis results from changes in kinetics or in abundance of proteins in signal transduction networks. Recently, it was shown that control of signalling cannot reside in a single gene product, and might well be dispersed over many components. Which of the reactions in these complex networks are most important, and ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208817
更新日期:2005-08-25 00:00:00
abstract::Soft tissue sarcomas are a heterogeneous group of neoplasms with various histological subtypes. Up to now, no individual causal molecular markers for prognosis and therapeutic success have been identified. A tumorigenic connection between the oncogene product Mdm2 and tumor suppressor p53 is generally accepted, but th...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201646
更新日期:1998-03-05 00:00:00
abstract::A dominant negative mutant of Ras, M17 Ras, was used to study the role of Ras in receptor coupling of Raf-1 and B-Raf protein serine/threonine kinases (PSKs). We found that mutant Ras blocks serum- and 12-O-tetradecanoyl phorbol 13-acetate-induced activation of Raf-1 kinase in NIH3T3 cells and Raf-1 as well as B-Raf P...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::The long-term cellular response to DNA damage is controlled by the tumor suppressor p53. It results in cell-cycle arrest followed by DNA repair and, depending on the degree of damage inflicted, premature senescence or apoptotic cell death. Here we show that in normal diploid fibroblasts the ubiquitin ligase anaphase-p...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.99
更新日期:2010-06-17 00:00:00
abstract::Topors was identified recently as a human protein that binds to topoisomerase I and p53. Topors contains a highly conserved RING domain and localizes in promyelocytic leukemia nuclear bodies. Relatively little is known regarding topors expression patterns or function. We now demonstrate that topors mRNA and protein ar...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207700
更新日期:2004-07-08 00:00:00
abstract::Cells in culture become competent to replicate in the absence of growth factor after progressing beyond the late G1 restriction point, suggesting that a set of genes expressed during G1 phase is sufficient to trigger completion of the cell cycle. However, this has not been demonstrated in an in vivo system. In this st...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204248
更新日期:2001-04-05 00:00:00
abstract::TNFα is a pleiotropic cytokine which fuels tumor cell growth, invasion, and metastasis in some malignancies, while in others it induces cytotoxic cell death. However, the molecular mechanism by which TNFα exerts its diverse effects on breast cancer subtypes remains elusive. Using in vitro assays and mouse xenografts, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0472-0
更新日期:2019-01-01 00:00:00
abstract::We recently reported an interaction between the p14(ARF) protein and human topoisomerase I (Topo I) resulting in the stimulation of the relaxation activity of Topo I. Our data showed that the complex between the two proteins was located within the nucleolus. In the present work, we have investigated the regions of p14...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206214
更新日期:2003-04-03 00:00:00
abstract::As tumors grow and invade beyond their homeostatic limits, the tumor cells are subjected to insufficient nutrient and oxygen supplies because of excessive demand for nutrition and oxygen, and insufficient vascularization. We therefore hypothesized that tolerance to nutrient deprivation as well as angiogenesis may be c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205737
更新日期:2002-09-05 00:00:00
abstract::Anaplastic lymphoma kinase (ALK) was originally identified from a rare subtype of non-Hodgkin's lymphomas carrying t(2;5)(p23;q35) translocation, where ALK was constitutively activated as a result of a fusion with nucleophosmin (NPM). Aberrant ALK fusion proteins were also generated in inflammatory fibrosarcoma and a ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.616
更新日期:2012-11-01 00:00:00