Elevated interleukin-6 and G-CSF in human pancreatic cancer cell conditioned medium suppress dendritic cell differentiation and activation.

Abstract:

:Although dendritic cell (DC) function is impaired in pancreatic cancer patients, the underlying mechanisms are unknown. This study analyzed the soluble factors released by pancreatic cancer cells responsible for inhibiting DC differentiation and activation. Medium conditioned by a highly metastatic human pancreatic cancer cell line BxPC-3 [BxPC-3 conditioned medium (BxCM)] was mainly used for the study. Both CD34+ hematopoietic progenitor cell-derived and CD14+ monocyte-derived immature DCs and mature DCs (mDCs) were inhibited by BxCM. Allostimulation of CD4+ and CD8+ T cells by BxCM-treated mDCs was inefficient and resulted in production of lower levels of Th1 and Th2 cytokines. Antigen-specific T-cell activation capability was also reduced in BxCM-treated mDCs. Addition of exogenous interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF), which were present in high amounts in BxCM, mimicked the inhibitory effect of BxCM on DC differentiation and maturation. IL-6 was able to suppress DC differentiation and G-CSF mainly acted on the suppressing allostimulatory capacity of DCs. In addition, pancreatic cancer patient sera were able to inhibit DC differentiation of CD14+ monocytes obtained from healthy donors. Depleting IL-6 or G-CSF from BxCM could reverse the DC-inhibitory properties of BxCM. Furthermore, BxCM, IL-6, or G-CSF led to the activation of signal transducer and activator of transcription 3 (STAT3) in CD14+ monocytes to different degrees. Blocking BxCM-induced STAT3 activation also reversed the inhibitory effect of BxCM on DC differentiation. Therefore, IL-6 and G-CSF in BxCM represent two main factors responsible for suppression of DC differentiation, maturation, and antigen presentation, and this suppression of DC functions may be due to the aberrant activation of STAT3 by BxCM.

journal_name

Cancer Res

journal_title

Cancer research

authors

Bharadwaj U,Li M,Zhang R,Chen C,Yao Q

doi

10.1158/0008-5472.CAN-06-3963

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

5479-88

issue

11

eissn

0008-5472

issn

1538-7445

pii

67/11/5479

journal_volume

67

pub_type

杂志文章
  • Gonadal protection and fecundity rates in cyclophosphamide-treated rats.

    abstract::Premature ovarian failure and reduced fecundity are well-documented consequences of cytotoxic chemotherapy used to treat patients with malignant diseases. To investigate the ability of different hormonal agents to block the effects of cyclophosphamide (CTX) on reproductive function, sexually mature female Long-Evans r...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Montz FJ,Wolff AJ,Gambone JC

    更新日期:1991-04-15 00:00:00

  • Isolation and characterization of complementary DNA to proliferating cell nucleolar antigen P40.

    abstract::Proliferating cell nucleolar antigen P40 is a late G1-specific protein, which was found in a variety of human tumors (A. Chatterjee, J. W. Freeman, and H. Busch. Cancer Res., 47: 1123-1129, 1987). Two overlapping complementary DNA clones for antigen P40 were isolated by immunoscreening a lambda gt11 human expression l...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Reddy AB,Chatterjee A,Rothblum LI,Black A,Busch H

    更新日期:1989-04-01 00:00:00

  • Infrequent inactivation of the retinoblastoma gene despite frequent loss of chromosome 13q in head and neck squamous cell carcinoma.

    abstract::Our recent allelic analysis of head and neck squamous cell carcinomas identified a high incidence of chromosomal loss on 13q. To further define an area of minimal loss, we tested 60 primary head and neck squamous cell carcinomas in 59 patients for loss of heterozygosity (LOH) by using 10 polymorphic microsatellite mar...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yoo GH,Xu HJ,Brennan JA,Westra W,Hruban RH,Koch W,Benedict WF,Sidransky D

    更新日期:1994-09-01 00:00:00

  • Lipid-dependent proliferation of pancreatic cancer cell lines.

    abstract::Capan 1, a human pancreatic cancer cell line, is routinely grown in 10% fetal calf serum (FCS). In order to characterize the factors needed for its proliferation, FCS was replaced by a synthetic serum (Ultroser G). For Capan 1 proliferation we found that Ultroser G was as efficient as FCS. A subfraction of Ultroser G ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Clerc P,Bensaadi N,Pradel P,Estival A,Clemente F,Vaysse N

    更新日期:1991-07-15 00:00:00

  • Anticachectic effects of formoterol: a drug for potential treatment of muscle wasting.

    abstract::In cancer cachexia both cardiac and skeletal muscle suffer an important protein mobilization as a result of increased proteolysis. Administration of the beta2-agonist formoterol to both rats and mice bearing highly cachectic tumors resulted in an important reversal of the muscle-wasting process. The anti-wasting effec...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-0425

    authors: Busquets S,Figueras MT,Fuster G,Almendro V,Moore-Carrasco R,Ametller E,Argilés JM,López-Soriano FJ

    更新日期:2004-09-15 00:00:00

  • Characterization of trimetrexate transport in human lymphoblastoid cells and development of impaired influx as a mechanism of resistance to lipophilic antifolates.

    abstract::The purpose of this study was to characterize the transport properties of trimetrexate in WI-L2 human lymphoblastoid cells and determine the mode of resistance that had developed in a subline, WI-L2/TMQ, that was grown in increasing concentrations of trimetrexate. WI-L2/TMQ cells were 62-fold resistant to trimetrexate...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Fry DW,Besserer JA

    更新日期:1988-12-15 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

  • Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma.

    abstract::This study was undertaken to determine the extent of apoptosis in lung carcinoma and to evaluate it as a prognostic marker. A series of 75 lung carcinomas (47 squamous cell carcinomas, 24 adenocarcinomas, 3 small cell carcinomas, and 1 large cell carcinoma) was analyzed for the extent of apoptosis by using the 3' end-...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Törmänen U,Eerola AK,Rainio P,Vähäkangas K,Soini Y,Sormunen R,Bloigu R,Lehto VP,Pääkkö P

    更新日期:1995-12-01 00:00:00

  • Phase I trial of the amsacrine analogue 9-[( 2-methoxy-4-[(methylsulfonyl)amino]-phenyl]amino)-N,5-dimethyl-4- acridinecarboxamide (CI-921).

    abstract::CI-921, an analogue of amsacrine with superior activity against in vivo and in vitro experimental tumor models, has been studied in 16 patients with solid tumors refractory to chemotherapy or for which conventional therapy does not exist. Thirty-nine cycles were given and doses escalated from 39 to 810 mg/m2. This tot...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hardy JR,Harvey VJ,Paxton JW,Evans P,Smith S,Grove W,Grillo-Lopez AJ,Baguley BC

    更新日期:1988-11-15 00:00:00

  • Deacetylase activity of human tumor cells producing immunosuppressive aminosugars: its possible role in resistance to cell-mediated cytotoxicity.

    abstract::In the present study, we examined the presence of deacetylases capable of producing free hexosamines, which we have shown earlier to be immunosuppressive against human natural killer (NK) cell-mediated cytotoxicity, from N-acetylhexosamines in human tumor cells. When human NK-resistant colon cancer cells (Colo-320DM) ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yagita M,Seppo A,Renkonen O,Saksela E

    更新日期:1993-12-01 00:00:00

  • Erythropoietin-induced polycythemia in athymic mice following transplantation of a human renal carcinoma cell line.

    abstract::An established cloned human renal carcinoma line RC-1, which has been continuously maintained in culture for several years and which produces erythropoietin, was injected s.c. into BALB/c athymic mice and produced tumors. Tumorigenicity was directly correlated with the number of RC-1 cells inoculated. Tumor cell histo...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Shouval D,Anton M,Galun E,Sherwood JB

    更新日期:1988-06-15 00:00:00

  • Membrane-associated glycoprotein (gp 160) identified on human lung tumors by a monoclonal antibody.

    abstract::A monoclonal antibody (5E8) has been used to identify and structurally characterize a previously unreported macromolecule present on the surface of human lung tumors. This antibody was derived from a hybrid clone that was produced using spleen cells of mice immunized with a surgically excised squamous cell carcinoma. ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Zylstra S,Chen FA,Ghosh SK,Repasky EA,Rao U,Takita H,Bankert RB

    更新日期:1986-12-01 00:00:00

  • Preparation of permanent slides of intact soft-agar colony cultures of hematopoietic and tumor stem cells.

    abstract::A simple technique is described for fixing colony-containing layers of soft agar and drying them onto microscopic slides. The method is extrapolated from techniques used in immunology for permanent preservation of immunodiffusion or immunoelectrophoresis plates. Slides prepared in this fashion are eminently suitable f...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Salmon SE,Buick RN

    更新日期:1979-03-01 00:00:00

  • Functional activation of the estrogen receptor-α and aromatase by the HDAC inhibitor entinostat sensitizes ER-negative tumors to letrozole.

    abstract::Approximately 25% of breast cancers do not express the estrogen receptor-α (ERα) and consequently do not respond to endocrine therapy. In these tumors, ERα repression is often due to epigenetic modifications such as methylation and histone deacetylation. For this reason, we investigated the ability of the histone deac...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-2458

    authors: Sabnis GJ,Goloubeva O,Chumsri S,Nguyen N,Sukumar S,Brodie AM

    更新日期:2011-03-01 00:00:00

  • Activity of mitozolomide (NSC 353451), a new imidazotetrazine, against xenografts from human melanomas, sarcomas, and lung and colon carcinomas.

    abstract::The chemosensitivity of human tumor xenografts to mitozolomide, 8-carbamoyl-3-(2-chloroethyl)imidazo[5-1-d]-1,2,3,5-tetrazin-4(3H) -one, was studied in 3 different assay systems. In concentrations of 1 to 500 micrograms/ml, mitozolomide completely inhibited the colony-forming ability in soft agar of cell suspensions f...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Fodstad O,Aamdal S,Pihl A,Boyd MR

    更新日期:1985-04-01 00:00:00

  • TSP50 encodes a testis-specific protease and is negatively regulated by p53.

    abstract::Earlier studies suggested that TSP50 is a testis-specific gene that encodes a protein, which is homologous to serine proteases but differs in that threonine replaces serine in its catalytic triad. Most importantly, it was abnormally reactivated in many breast cancer biopsies tested. While further investigating its bio...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3688

    authors: Xu H,Shan J,Jurukovski V,Yuan L,Li J,Tian K

    更新日期:2007-02-01 00:00:00

  • Analysis of BRAF and N-RAS mutations in metastatic melanoma tissues.

    abstract::We examined mutations in BRAF exons 11 and 15 and N-RAS exons 2 and 3, in 77 metastatic melanoma cases and 11 melanoma cell lines. Significant differences in the mutation rates observed at different metastatic sites could not be detected. The most frequent mutation, the V599E amino acid substitution in BRAF exon 15, w...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gorden A,Osman I,Gai W,He D,Huang W,Davidson A,Houghton AN,Busam K,Polsky D

    更新日期:2003-07-15 00:00:00

  • Predictive Signatures Inform the Effective Repurposing of Decitabine to Treat KRAS-Dependent Pancreatic Ductal Adenocarcinoma.

    abstract::Mutated KRAS protein is a pivotal tumor driver in pancreatic cancer. However, despite comprehensive efforts, effective therapeutics that can target oncogenic KRAS are still under investigation or awaiting clinical approval. Using a specific KRAS-dependent gene signature, we implemented a computer-assisted inspection o...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-0187

    authors: Mottini C,Tomihara H,Carrella D,Lamolinara A,Iezzi M,Huang JK,Amoreo CA,Buglioni S,Manni I,Robinson FS,Minelli R,Kang Y,Fleming JB,Kim MP,Bristow CA,Trisciuoglio D,Iuliano A,Del Bufalo D,Di Bernardo D,Melisi D,Dra

    更新日期:2019-11-01 00:00:00

  • Gonadotropins activate proteolysis and increase invasion through protein kinase A and phosphatidylinositol 3-kinase pathways in human epithelial ovarian cancer cells.

    abstract::Despite evidence that gonadotropins may facilitate peritoneal metastasis of ovarian cancer by increasing cell adhesion, the action and molecular mechanism of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in ovarian cancer invasion is not well characterized. In the present study, we investigated the e...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-1785

    authors: Choi JH,Choi KC,Auersperg N,Leung PC

    更新日期:2006-04-01 00:00:00

  • A cascade of modules of a network defines cancer progression.

    abstract::Similar histologic subtypes of cancers often exhibit different spectrum of genetic and epigenetic alterations. The heterogeneity observed due to lack of consistent and defined alterations affecting a unique set of gene(s) or gene products in cancers derived from a specific tissue, or an organ, pose a challenge in unra...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-0993

    authors: Thiagalingam S

    更新日期:2006-08-01 00:00:00

  • Protein kinase C inhibition and x-linked inhibitor of apoptosis protein degradation contribute to the sensitization effect of luteolin on tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in cancer cells.

    abstract::Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an important member of the TNF superfamily with great potential in cancer therapy. Luteolin is a dietary flavonoid commonly found in some medicinal plants. Here we found that pretreatment with a noncytotoxic concentration of luteolin significantl...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3875

    authors: Shi RX,Ong CN,Shen HM

    更新日期:2005-09-01 00:00:00

  • Cellular and serum involvement in protection against Friend leukemia virus.

    abstract::Treatment of mice with the immunomodulator pyran copolymer inhibited leukemogenesis produced by Friend leukemia virus (FLV) complex, as evidenced by inhibition of the spleen focus-forming virus and lymphatic leukemia virus, as well as by a significant decrease in splenomegaly. In this report we present data suggesting...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Schuller GB,Morahan PS

    更新日期:1977-11-01 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

  • Detection of ataxia telangiectasia heterozygous cell lines by postirradiation cumulative labeling index: measurements with coded samples.

    abstract::Coded skin fibroblast cell strains from ataxia telangiectasia (AT) families and apparently normal individuals were obtained from two different sources. AT homozygous strains were clearly identified on the basis of marked hypersensitivity to cell killing by X-irradiation. AT heterozygotes were intermediate in their cyt...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Nagasawa H,Kraemer KH,Shiloh Y,Little JB

    更新日期:1987-01-15 00:00:00

  • Connexins act as tumor suppressors in three-dimensional mammary cell organoids by regulating differentiation and angiogenesis.

    abstract::Connexins are tumor suppressors, and human breast connexin 26 (Cx26) and connexin 43 (Cx43) gap junctions are often down-regulated in breast cancer. We previously showed that Cx26 and Cx43 overexpressed in MDA-MB-231 breast cancer cells inhibited tumor growth in vivo but not in two-dimensional cultures. In the current...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-4302

    authors: McLachlan E,Shao Q,Wang HL,Langlois S,Laird DW

    更新日期:2006-10-15 00:00:00

  • Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts.

    abstract::We have previously shown that topotecan, a topoisomerase I poison, inhibits hypoxia-inducible factor (HIF)-1alpha protein accumulation by a DNA damage-independent mechanism. Here, we report that daily administration of topotecan inhibits HIF-1alpha protein expression in U251-HRE glioblastoma xenografts. Concomitant wi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-2116

    authors: Rapisarda A,Zalek J,Hollingshead M,Braunschweig T,Uranchimeg B,Bonomi CA,Borgel SD,Carter JP,Hewitt SM,Shoemaker RH,Melillo G

    更新日期:2004-10-01 00:00:00

  • β-catenin activation in a novel liver progenitor cell type is sufficient to cause hepatocellular carcinoma and hepatoblastoma.

    abstract::Hepatocellular carcinoma (HCC) was thought historically to arise from hepatocytes, but gene expression studies have suggested that it can also arise from fetal progenitor cells or their adult progenitor progeny. Here, we report the identification of a unique population of fetal liver progenitor cells in mice that can ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-13-3275

    authors: Mokkapati S,Niopek K,Huang L,Cunniff KJ,Ruteshouser EC,deCaestecker M,Finegold MJ,Huff V

    更新日期:2014-08-15 00:00:00

  • Expression of the human T-cell-specific tyrosine kinase YT16 (lck) message in leukemic T-cell lines.

    abstract::To evaluate the role of the human T-cell-specific tyrosine kinase lck (YT16), we measured the levels of lck expression in thymocytes, peripheral T-cells, and leukemia T-cell lines which are arrested at different stages of thymic differentiation. The results indicate that higher levels of the lck message can be found i...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Koga Y,Kimura N,Minowada J,Mak TW

    更新日期:1988-02-15 00:00:00

  • High levels of dioxin-like potential in cigarette smoke evidenced by in vitro and in vivo biosensing.

    abstract::Cigarette smoke contains low levels of agonists for the aryl hydrocarbon receptor (AhR; also called the dioxin receptor). However, little is understood about the whole potential of cigarette smoke for activating AhR. In this report, we evaluated the total "dioxin-like" activity of cigarette smoke using in vitro and in...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-4541

    authors: Kasai A,Hiramatsu N,Hayakawa K,Yao J,Maeda S,Kitamura M

    更新日期:2006-07-15 00:00:00

  • Vascular endothelial growth factor contributes to the prostate cancer-induced osteoblast differentiation mediated by bone morphogenetic protein.

    abstract::Human prostate cancer has a high predisposition to metastasize to bone, resulting in the formation of osteoblastic metastases. The mechanism through which prostate cancer cells promote osteoblastic lesions is undefined. Vascular endothelial growth factor (VEGF) has been implicated as a mediator of osteoblast activity....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.can-03-1382

    authors: Dai J,Kitagawa Y,Zhang J,Yao Z,Mizokami A,Cheng S,Nör J,McCauley LK,Taichman RS,Keller ET

    更新日期:2004-02-01 00:00:00