Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer.

Abstract:

:The forkhead transcription factor Foxp3 is highly expressed in CD4+CD25+ regulatory T cells (Treg) and was recently identified as a key player in mediating their inhibitory functions. Here, we describe for the first time the expression and function of Foxp3 in pancreatic ductal adenocarcinoma cells and tumors. Foxp3 expression was induced by transforming growth factor-beta2 (TGF-beta2), but not TGF-beta1 stimulation in these cells, and was partially suppressed following antibody-mediated neutralization of TGF-beta2. The TGF-beta2 effect could be mimicked by ectopic expression of a constitutively active TGF-beta type I receptor/ALK5 mutant. Down-regulation of Foxp3 with small interfering RNA (siRNA) in pancreatic carcinoma cells resulted in the up-regulation of interleukin 6 (IL-6) and IL-8 expression, providing evidence for a negative transcriptional activity of Foxp3 also in these epithelial cells. Coculture of Foxp3-expressing tumor cells with naive T cells completely inhibited T-cell proliferation, but not activation, and this antiproliferative effect was partially abrogated following specific inhibition of Foxp3 expression. These findings indicate that pancreatic carcinoma cells share growth-suppressive effects with Treg and suggest that mimicking Treg function may represent a new mechanism of immune evasion in pancreatic cancer.

journal_name

Cancer Res

journal_title

Cancer research

authors

Hinz S,Pagerols-Raluy L,Oberg HH,Ammerpohl O,Grüssel S,Sipos B,Grützmann R,Pilarsky C,Ungefroren H,Saeger HD,Klöppel G,Kabelitz D,Kalthoff H

doi

10.1158/0008-5472.CAN-06-3304

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

8344-50

issue

17

eissn

0008-5472

issn

1538-7445

pii

67/17/8344

journal_volume

67

pub_type

杂志文章
  • p53-Altered FBXW7 expression determines poor prognosis in gastric cancer cases.

    abstract::A molecular target associated with the progression of gastric cancer has not yet been uncovered. FBXW7 is a tumor suppressor gene transcriptionally controlled by p53 that plays a role in the regulation of cell cycle exit and reentry via c-Myc degradation. Few studies have addressed the clinical significance of FBXW7 e...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-2846

    authors: Yokobori T,Mimori K,Iwatsuki M,Ishii H,Onoyama I,Fukagawa T,Kuwano H,Nakayama KI,Mori M

    更新日期:2009-05-01 00:00:00

  • miR145 targets the SOX9/ADAM17 axis to inhibit tumor-initiating cells and IL-6-mediated paracrine effects in head and neck cancer.

    abstract::ALDH1(+)CD44(+) cells are putative tumor-initiating cells (TIC) in head and neck squamous cell carcinomas (HNC). miR-145 regulates tumorigenicity in various cancers but the breadth of its mechanistic contributions and potential therapeutic applications are not completely known. Here, we report that ALDH1(+)CD44(+)-HNC...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-3840

    authors: Yu CC,Tsai LL,Wang ML,Yu CH,Lo WL,Chang YC,Chiou GY,Chou MY,Chiou SH

    更新日期:2013-06-01 00:00:00

  • Overexpression of DNA polymerase beta sensitizes mammalian cells to 2',3'-deoxycytidine and 3'-azido-3'-deoxythymidine.

    abstract::Mammalian DNA polymerase beta is a DNA repair enzyme expressed constitutively at a low level. In vitro, purified DNA polymerase (Pol) beta incorporates the nucleotide analogues 2'-3' deoxycytidine (ddC)-triphosphate and 3'-azido-3'-deoxythymidine (AZT)-triphosphate into DNA, causing chain termination. We have tested t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bouayadi K,Hoffmann JS,Fons P,Tiraby M,Reynes JP,Cazaux C

    更新日期:1997-01-01 00:00:00

  • Nitric oxide in physiologic concentrations targets the translational machinery to increase the proliferation of human breast cancer cells: involvement of mammalian target of rapamycin/eIF4E pathway.

    abstract::Nitric oxide (NO) in nanomolar (nmol/L) concentrations is consistently detected in tumor microenvironment and has been found to promote tumorigenesis. The mechanism by which NO enhances tumor progression is largely unknown. In this study, we investigated the possible mechanisms and identified cellular targets by which...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-4623

    authors: Pervin S,Singh R,Hernandez E,Wu G,Chaudhuri G

    更新日期:2007-01-01 00:00:00

  • Cell cycle modulation by a multitargeted antifolate, LY231514, increases the cytotoxicity and antitumor activity of gemcitabine in HT29 colon carcinoma.

    abstract::The proliferation rate of HT29 colon carcinoma cells was decreased by the multitargeted antifolate (MTA), LY231514. This effect correlated with a buildup of cells near the G1-S interface after 24 h of incubation, and a synchronized progression of the population through S phase during the next 24 h. MTA treatment (0.03...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Tonkinson JL,Worzalla JF,Teng CH,Mendelsohn LG

    更新日期:1999-08-01 00:00:00

  • Immunohistochemical evidence of urokinase-type plasminogen activator in primary and metastatic tumors of pulmonary adenocarcinoma.

    abstract::The urokinase-type plasminogen activator (u-PA) was used to study 96 cases of lung adenocarcinoma and 49 cases of lymph node metastatic adenocarcinoma. We made use of the immunohistochemistry of paraffinized samples. u-PA was detected in the cytoplasm of tumor cells, and the number of positive cells was higher in pati...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Oka T,Ishida T,Nishino T,Sugimachi K

    更新日期:1991-07-01 00:00:00

  • Luteolin inhibits vascular endothelial growth factor-induced angiogenesis; inhibition of endothelial cell survival and proliferation by targeting phosphatidylinositol 3'-kinase activity.

    abstract::In an attempt to identify phytochemicals contributing to the well-documented preventive effect of plant-based diets on cancer incidence and mortality, we have previously shown that certain flavonoids inhibit in vitro angiogenesis. Here, we show that the flavonoid luteolin inhibited tumor growth and angiogenesis in a m...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-03-3104

    authors: Bagli E,Stefaniotou M,Morbidelli L,Ziche M,Psillas K,Murphy C,Fotsis T

    更新日期:2004-11-01 00:00:00

  • Factors affecting the expression of carcinoembryonic antigen at the surface of cultured human colon carcinoma cells.

    abstract::Factors affecting the expression of carcinoembryonic antigen (CEA) at the surface of in vitro human colon carcinoma cells were determined using 125I-labeled antibodies. Binding of specific anti-CEA antibodies resulted in polar redistribution of CEA, followed by endocytosis of most of the CEA-anti-CEA complexes. These ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Rosenthal KL,Tompkins WA,Rawls WE

    更新日期:1980-12-01 00:00:00

  • Decreased activation of carcinogens in the liver of carcinogen-resistant rats.

    abstract::We have developed a new strain of rats (resistant rat) which exhibit resistance against the carcinogenic action of several carcinogenic compounds. In the present study, we compared the ability of resistant rat liver to activate 3'-methyl-4-dimethylaminoazobenzene and 2-acetylaminofluorene to highly reactive metabolite...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yano M,Higashi T,Kano S,Tateishi N,Kido Y,Mori T,Higashi K,Sakamoto Y

    更新日期:1989-10-01 00:00:00

  • Thrombospondin-1 type 1 repeat recombinant proteins inhibit tumor growth through transforming growth factor-beta-dependent and -independent mechanisms.

    abstract::Thrombospondin-1 (TSP-1) is a potent inhibitor of tumor growth and angiogenesis. The antiangiogenic activity of TSP-1 has been mapped to the procollagen homology region and the type 1 repeats (TSR) using synthetic peptides. To elucidate the molecular mechanisms that are involved in the inhibition of tumor growth by th...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Miao WM,Seng WL,Duquette M,Lawler P,Laus C,Lawler J

    更新日期:2001-11-01 00:00:00

  • Cell surface characteristics of an allotransplantable TA3 ascites subline resulting from a process of immunoselection.

    abstract::Comparison of the cell surface characteristics of the parental strain-specific TA3-St ascites cell (I) of the strain A mouse and the more allotransplantable TA3-St/ticol ascites cell (II), immunoselected for reduced absorption of anti-H-2a antibody from Cell I, revealed the following. Cell II, like Cell I, possessed n...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Codington JF,Das HR,Dalianis T,Klein G,Miller SC,Silber C,Lampert LA,Darby DM,Jeanloz RW

    更新日期:1983-09-01 00:00:00

  • The plexin-A1 receptor activates vascular endothelial growth factor-receptor 2 and nuclear factor-kappaB to mediate survival and anchorage-independent growth of malignant mesothelioma cells.

    abstract::The semaphorins and their receptors, the neuropilins and the plexins, are constituents of a complex regulatory system that controls axonal guidance. Moreover, many types of tumor cells express various members of semaphorins and receptors, but the biological activities within tumor mass and the signal transduction mech...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-3659

    authors: Catalano A,Lazzarini R,Di Nuzzo S,Orciari S,Procopio A

    更新日期:2009-02-15 00:00:00

  • Suppression of human prostate tumor growth in mice by a cytolytic D-, L-amino Acid Peptide: membrane lysis, increased necrosis, and inhibition of prostate-specific antigen secretion.

    abstract::Gene-encoded host defense peptides are used as part of the innate immunity, and many of them act by directly lysing the cell membrane of the pathogen. A few of these peptides showed anticancer activity in vitro but could not be used in vivo because of their inactivation by serum. We designed a 15-amino acid peptide, c...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-1438

    authors: Papo N,Braunstein A,Eshhar Z,Shai Y

    更新日期:2004-08-15 00:00:00

  • Combination of anastrozole with fulvestrant in the intratumoral aromatase xenograft model.

    abstract::Although the aromatase inhibitor anastrozole has been shown to be very effective in the treatment of hormone-dependent postmenopausal breast cancer, some patients with advanced disease will develop resistance to treatment. To investigate therapeutic strategies to overcome resistance to anastrozole treatment, we have u...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-6807

    authors: Macedo LF,Sabnis GJ,Goloubeva OG,Brodie A

    更新日期:2008-05-01 00:00:00

  • Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells.

    abstract::Androgens via their receptor (AR) may play a role in prostate cancer etiology. This study focuses on the inhibitory effects of resveratrol on androgen action in the LNCaP prostate cancer cell line. We found that resveratrol represses different classes of androgen up-regulated genes at the protein or mRNA level includi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Mitchell SH,Zhu W,Young CY

    更新日期:1999-12-01 00:00:00

  • Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms.

    abstract::Single-chain antigen-binding proteins, or sFvs, represent potentially unique molecules for targeted delivery of drugs, toxins, or radionuclides to a tumor site. In previous studies (Cancer Res., 51:6363-6371, 1991) using a human colon carcinoma xenograft model, it was demonstrated that the sFv has an extremely rapid p...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yokota T,Milenic DE,Whitlow M,Schlom J

    更新日期:1992-06-15 00:00:00

  • TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming.

    abstract::Translocations fusing the strong androgen-responsive gene, TMPRSS2, with ERG or other oncogenic ETS factors may facilitate prostate cancer development. Here, we studied 18 advanced prostate cancers for ETS factor alterations, using reverse transcription-PCR and DNA and RNA array technologies, and identified putative E...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-1986

    authors: Iljin K,Wolf M,Edgren H,Gupta S,Kilpinen S,Skotheim RI,Peltola M,Smit F,Verhaegh G,Schalken J,Nees M,Kallioniemi O

    更新日期:2006-11-01 00:00:00

  • The palmitoylation of metastasis suppressor KAI1/CD82 is important for its motility- and invasiveness-inhibitory activity.

    abstract::The cancer metastasis suppressor protein KAI1/CD82 is a member of the tetraspanin superfamily. Recent studies have demonstrated that tetraspanins are palmitoylated and that palmitoylation contributes to the organization of tetraspanin webs or tetraspanin-enriched microdomains. However, the effect of palmitoylation on ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-1574

    authors: Zhou B,Liu L,Reddivari M,Zhang XA

    更新日期:2004-10-15 00:00:00

  • FGFR1 Induces Glioblastoma Radioresistance through the PLCγ/Hif1α Pathway.

    abstract::FGF2 signaling in glioblastoma induces resistance to radiotherapy, so targeting FGF2/FGFR pathways might offer a rational strategy for tumor radiosensitization. To investigate this possibility, we evaluated a specific role for FGFR1 in glioblastoma radioresistance as modeled by U87 and LN18 glioblastomas in mouse xeno...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-2058

    authors: Gouazé-Andersson V,Delmas C,Taurand M,Martinez-Gala J,Evrard S,Mazoyer S,Toulas C,Cohen-Jonathan-Moyal E

    更新日期:2016-05-15 00:00:00

  • Nuclear factor-kappaB p65 mediates tumor necrosis factor alpha-induced nuclear translocation of telomerase reverse transcriptase protein.

    abstract::Sustained proliferation of cancer cells requires telomerase to maintain telomeres that regulate chromosomal stability and cellular mitosis. Expression of human telomerase reverse transcriptase (hTERT) catalytic subunit, which modulates telomerase activity, is regulated at both the transcriptional level and via phospho...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Akiyama M,Hideshima T,Hayashi T,Tai YT,Mitsiades CS,Mitsiades N,Chauhan D,Richardson P,Munshi NC,Anderson KC

    更新日期:2003-01-01 00:00:00

  • Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines.

    abstract::The anticancer oxazaphosphorine prodrugs cyclophosphamide and ifosfamide are activated in human liver by a 4-hydroxylation reaction catalyzed by multiple cytochrome P450 (CYP) enzymes. In the present study, we used a cultured human hepatocyte model to identify possible inducers of the CYP-catalyzed activation of these...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Chang TK,Yu L,Maurel P,Waxman DJ

    更新日期:1997-05-15 00:00:00

  • Human breast cancer cell cycle synchronization by estrogens and antiestrogens in culture.

    abstract::The mechanisms by which estrogens and antiestrogens modulate breast cancer growth have not been totally defined. We have examined the cell cycle kinetic effects of estrogens and antiestrogens in cultured human breast cancer cell lines. In a previous study, we showed that tamoxifen induces a transition delay in early t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Osborne CK,Boldt DH,Estrada P

    更新日期:1984-04-01 00:00:00

  • Inactivation of the p53 tumor suppressor gene via a novel Alu rearrangement.

    abstract::Inactivation of the p53 tumor suppressor gene is a common finding in human cancer. In most cases, inactivation is due to a point mutation in the gene, but rearrangement of the p53 gene is sometimes observed. We analyzed the inactivation of p53 in the human pancreas cancer cell line Hs766T, which harbors a structural a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Slebos RJ,Resnick MA,Taylor JA

    更新日期:1998-12-01 00:00:00

  • DNA mismatch binding defects, DNA damage tolerance, and mutator phenotypes in human colorectal carcinoma cell lines.

    abstract::DNA mismatch binding in vitro, resistance to DNA methylation damage, and spontaneous mutation rates were examined in human colorectal adenocarcinoma cell lines. Of 11 cell lines, 3 (DLD1, HCT15, and LoVo) were defective in mismatch binding. All three lines had a mutator phenotype. These properties indicate that DLD1 a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Branch P,Hampson R,Karran P

    更新日期:1995-06-01 00:00:00

  • miR-483-5p promotes invasion and metastasis of lung adenocarcinoma by targeting RhoGDI1 and ALCAM.

    abstract::The nodal regulatory properties of microRNAs (miRNA) in metastatic cancer may offer new targets for therapeutic control. Here, we report that upregulation of miR-483-5p is correlated with the progression of human lung adenocarcinoma. miR-483-5p promotes the epithelial-mesenchymal transition (EMT) accompanied by invasi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-13-2193

    authors: Song Q,Xu Y,Yang C,Chen Z,Jia C,Chen J,Zhang Y,Lai P,Fan X,Zhou X,Lin J,Li M,Ma W,Luo S,Bai X

    更新日期:2014-06-01 00:00:00

  • Immunofluorescent analysis of expression of the RNA tumor virus major glycoprotein, gp71, on the surfaces of normal murine cells.

    abstract::The expression of the major glycoprotein, gp71, of murine leukemia virus was studied on the surfaces of a variety of normal murine cell lines with a monospecific rabbit antiserum raised against purified Friend murine leukemia virus gp71. Using viable cell membrane immunofluorescence, most established and early passage...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Cloyd MW,Bolognesi DP,Bigner DD

    更新日期:1977-03-01 00:00:00

  • Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb.

    abstract::Progression of the eukaryotic cell division cycle is regulated by a series of structurally related serine/threonine protein kinases known as cyclin-dependent kinases (CDKs). The D-type cyclin-dependent kinases, CDK4 and CDK6, have been strongly implicated in the control of G1 progression and the phosphorylation of the...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Li Y,Nichols MA,Shay JW,Xiong Y

    更新日期:1994-12-01 00:00:00

  • Sequential alterations in growth control and cell dynamics of rat hepatocytes in early precancerous steps in hepatocarcinogenesis.

    abstract::This set of experiments is the second of a series designed to explore alterations in cell dynamics and growth control of new populations of hepatocytes that appear to play a role in the carcinogenic process induced in the liver by chemical carcinogens. This is part of an ongoing study of the biochemical and molecular ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Rotstein J,Sarma DS,Farber E

    更新日期:1986-05-01 00:00:00

  • Chemical enhancers of cytokine signaling that suppress microfilament turnover and tumor cell growth.

    abstract::The transforming growth factor-beta (TGF-beta) family of cytokines regulates cell proliferation, morphogenesis, and specialized cell functions in metazoans. Herein, we screened a compound library for modifiers of TGF-beta signaling in NMuMG epithelial cells using a cell-based assay to measure Smad2/3 nuclear transloca...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-2542

    authors: Park HJ,Partridge E,Cheung P,Pawling J,Donovan R,Wrana JL,Dennis JW

    更新日期:2006-04-01 00:00:00

  • Trp53 inactivation in the tumor microenvironment promotes tumor progression by expanding the immunosuppressive lymphoid-like stromal network.

    abstract::Inactivation of the tumor suppressor p53 through somatic mutations, observed in 50% of human cancers, is one of the leading causes of tumorigenesis. Clinical and experimental evidence also reveals that p53 mutations sometimes occur in tumor-associated fibroblasts, which correlate with an increased rate of metastases a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-3810

    authors: Guo G,Marrero L,Rodriguez P,Del Valle L,Ochoa A,Cui Y

    更新日期:2013-03-15 00:00:00