CXCL5 contributes to tumor metastasis and recurrence of intrahepatic cholangiocarcinoma by recruiting infiltrative intratumoral neutrophils.

Abstract:

:CXCL5 is a member of the CXC-type chemokine family that may play a role in carcinogenesis and cancer progression. This study investigates the biological function and clinical significance of CXCL5 in intrahepatic cholangiocarcinoma (ICC). We demonstrated that CXCL5 was overexpressed in ICC cell lines and tumor samples compared with paired normal tissues. CXCL5 had a direct chemoattractant effect on neutrophils in vitro through PI3K-Akt and extracellular signal-regulated kinase 1/2 signaling pathways. In animal studies, CXCL5 promoted tumor growth and metastasis without altering in vitro proliferative and invasive ability of ICC cells, and this effect was mediated by the recruitment of intratumoral infiltrative neutrophils by tumor-derived CXCL5. Immunohistochemical analysis of ICC samples showed that overexpression of CXCL5 correlated strongly with intratumoral neutrophil infiltration, shorter overall survival and high tumor recurrence. Multivariate analysis revealed that CXCL5 overexpression alone, or combined with the presence of intratumoral neutrophils, was an independent prognostic indicator for ICC. In conclusion, our data showed that CXCL5 promotes ICC growth and metastasis by recruiting intratumoral neutrophils. CXCL5 alone or combined with intratumoral neutrophils is a novel prognostic predictor for ICC patients and a potential therapeutic target.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Zhou SL,Dai Z,Zhou ZJ,Chen Q,Wang Z,Xiao YS,Hu ZQ,Huang XY,Yang GH,Shi YH,Qiu SJ,Fan J,Zhou J

doi

10.1093/carcin/bgt397

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

597-605

issue

3

eissn

0143-3334

issn

1460-2180

pii

bgt397

journal_volume

35

pub_type

杂志文章
  • Cooperation of bcl-2 and myc in the neoplastic transformation of normal rat liver epithelial cells is related to the down-regulation of gap junction-mediated intercellular communication.

    abstract::The objectives of this study were to isolate several rat liver epithelial cell clones containing the human bcl-2 and myc/bcl-2 genes in order to study their potential cooperative effect on neoplastic transformation and gap junction-mediated intercellular communication (GJIC) and to test the hypothesis that the loss of...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:

    authors: DeoCampo ND,Wilson MR,Trosko JE

    更新日期:2000-08-01 00:00:00

  • Chemopreventive effect of S-allylcysteine and its relationship to the detoxification enzyme glutathione S-transferase.

    abstract::Sulfur-containing substances derived from garlic and onion have been shown to prevent experimental carcinogenesis. One of the hypotheses explaining the mechanisms of the chemopreventive activity of these substances is that they activate detoxification systems such as glutathione S-transferase (GST). In this study the ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.5.1041

    authors: Hatono S,Jimenez A,Wargovich MJ

    更新日期:1996-05-01 00:00:00

  • Tocopherols inhibit estrogen-induced cancer stemness and OCT4 signaling in breast cancer.

    abstract::Estrogen plays an important role in breast cancer development. While the mechanism of the estrogen effects is not fully elucidated, one possible route is by increasing the stem cell-like properties in the tumors. Tocopherols are known to reduce breast cancer development and progression. The aim of the present study is...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgy071

    authors: Bak MJ,Furmanski P,Shan NL,Lee HJ,Bao C,Lin Y,Shih WJ,Yang CS,Suh N

    更新日期:2018-07-30 00:00:00

  • Diallyl disulfide inhibits p34(cdc2) kinase activity through changes in complex formation and phosphorylation.

    abstract::Previous studies from our laboratory demonstrated that diallyl disulfide (DADS), an oil-soluble allyl sulfur compound found in processed garlic, markedly suppressed p34(cdc2) kinase activity and induced a G(2)/M phase arrest in cultured human colon tumor (HCT-15) cells. The present studies reveal that suppression of p...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:

    authors: Knowles LM,Milner JA

    更新日期:2000-06-01 00:00:00

  • Bioactivation of N-nitrosopiperidine to mutagens: role of hepatic cytochrome P-450 proteins and contribution of cytosolic fraction.

    abstract::In the present study the role of two families of cytochrome P-450 proteins and the contribution of the cytosolic fraction in the activation of N-nitrosopiperidine to mutagens in the Ames test were investigated. The bioactivation of this nitrosamine was preferentially catalysed by the phenobarbitone-induced cytochromes...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.11.1691

    authors: Ayrton AD,Smith JN,Ioannides C

    更新日期:1987-11-01 00:00:00

  • The DNA binding activity of the liver transcription factors LFB1 (HNF1) and HNF4 varies coordinately in rat hepatocellular carcinoma.

    abstract::As renal cell carcinomas are characterized by the disappearance of the transcription factor LFB1, which is known to be primarily involved in gene regulation in the liver, we have measured the presence of LFB1 in rat hepatocellular carcinomas induced by diethylnitrosamine. The level of LFB1 binding activity in adenoid-...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.1.143

    authors: Stumpf H,Senkel S,Rabes HM,Ryffel GU

    更新日期:1995-01-01 00:00:00

  • Structure-activity relationships for epidermal ornithine decarboxylase induction and skin tumor promotion by anthrones.

    abstract::The present study was designed to compare the skin tumor promoting and epidermal ornithine decarboxylase (ODC) inducing activities of various structural analogs of anthralin (1,8-dihydroxy-9-anthrone) and chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone). Groups of 30 SENCAR mice each were initiated with 7,12-dimethylbe...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/9.8.1437

    authors: DiGiovanni J,Kruszewski FH,Coombs MM,Bhatt TS,Pezeshk A

    更新日期:1988-08-01 00:00:00

  • Tissue distribution and macromolecular binding of extremely low doses of [14C]-benzene in B6C3F1 mice.

    abstract::The tissue distribution and macromolecular binding of benzene was studied over a dose range spanning nine-orders of magnitude to determine the nature of the dose-response and to establish benzene's internal dosimetry at doses encompassing human environmental exposures. [14C]-Benzene was administered to B6C3F1 male mic...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/18.12.2421

    authors: Creek MR,Mani C,Vogel JS,Turteltaub KW

    更新日期:1997-12-01 00:00:00

  • Oncogenic transformation of human ovarian surface epithelial cells with defined cellular oncogenes.

    abstract::Ovarian surface epithelium (OSE) is considered to give rise to epithelial ovarian carcinomas (EOCs). To elucidate early processes contributing to the development of EOCs from the OSE, two batches of primary human OSE cells were transduced with non-viral human genes (mutant Cdk4, cyclinD1 and hTERT) so as to efficientl...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgp007

    authors: Sasaki R,Narisawa-Saito M,Yugawa T,Fujita M,Tashiro H,Katabuchi H,Kiyono T

    更新日期:2009-03-01 00:00:00

  • The effects of alternating dietary restriction and ad libitum feeding of mice on the development of diethylnitrosamine-induced liver tumours and its correlation to insulinaemia.

    abstract::The effects of alternating ad libitum feeding and 30% restriction of the dietary intake on the development of diethylnitrosamine (DEN)-induced hepatic neoplasia were investigated. Dietary restriction retarded the growth of glucose-6-phosphatase-deficient (G6Pd) preneoplastic foci and subsequently that of hepatocellula...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/12.2.311

    authors: Lagopoulos L,Sunahara GI,Würzner H,Dombrowsky I,Stalder R

    更新日期:1991-02-01 00:00:00

  • Quandtitative correlation among DNA damaging potency of six N-nitroso compounds and their potency in inducing tumor growth an bacterial mutations.

    abstract::Six N-nitroso compounds (N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodi-n-propylamine, N-nitroso-N-methylurea, N-nitrosopyrrolidine, and N-nitrosodi-n-butylamine) were tested in rats for liver DNA damaging activity by the alkaline elution technique. On molar basis their DNA damaging potency was found to de...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/2.5.425

    authors: Brambilla G,Cavanna M,Pino A,Robbiano L

    更新日期:1981-01-01 00:00:00

  • Sp1 and p73 activate PUMA following serum starvation.

    abstract::p53-upregulated modulator of apoptosis (PUMA) plays an essential role in p53-dependent apoptosis following DNA damage. PUMA also mediates apoptosis independent of p53. In this study, we investigated the role and mechanism of PUMA induction in response to serum starvation in p53-deficient cancer cells. Following serum ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn150

    authors: Ming L,Sakaida T,Yue W,Jha A,Zhang L,Yu J

    更新日期:2008-10-01 00:00:00

  • o-Nitrotoluene-induced large intestinal tumors in B6C3F1 mice model human colon cancer in their molecular pathogenesis.

    abstract::In the previous 500 2-year chemical bioassays within the National Toxicology Program, large intestinal tumors (cecal carcinomas) related to chemical exposure have not been observed in B6C3F1 mice. The recently completed o-nitrotoluene study provided the first cecal tumor response and an opportunity to evaluate the mor...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgh044

    authors: Sills RC,Hong HL,Flake G,Moomaw C,Clayton N,Boorman GA,Dunnick J,Devereux TR

    更新日期:2004-04-01 00:00:00

  • Suppression of azoxymethane-induced rat colon carcinogenesis by dietary administration of naturally occurring xanthophylls astaxanthin and canthaxanthin during the postinitiation phase.

    abstract::The modulating effects of dietary feeding of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) during the postinitiation phase on colon carcinogenesis initiated with azoxymethane (AOM) were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.12.2957

    authors: Tanaka T,Kawamori T,Ohnishi M,Makita H,Mori H,Satoh K,Hara A

    更新日期:1995-12-01 00:00:00

  • A variant in the CHEK2 promoter at a methylation site relieves transcriptional repression and confers reduced risk of lung cancer.

    abstract::Checkpoint kinase (CHEK) 2, a tumor suppressor gene, plays an essential role in the DNA damage checkpoint response cascade. We first investigated two polymorphisms in the proximal promoter of the CHEK2 gene and evaluated their associations with the risk of lung cancer in a case-control study using 500 incident lung ca...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgq089

    authors: Zhang S,Lu J,Zhao X,Wu W,Wang H,Lu J,Wu Q,Chen X,Fan W,Chen H,Wang F,Hu Z,Jin L,Wei Q,Shen H,Huang W,Lu D

    更新日期:2010-07-01 00:00:00

  • Phosphorylation of carcinogen metabolizing enzymes: regulation of the phosphorylation status of the major phenobarbital inducible cytochromes P-450 in hepatocytes.

    abstract::We present data showing that the major phenobarbital inducible cytochromes P-450 (cytochrome P-450IIB1 and cytochrome P-450IIB2) were phosphorylated in intact hepatocytes. This phosphorylation was greatly increased by the cAMP derivatives N6-dibutyryl-cAMP and 8-thiomethyl-cAMP mediated by a cAMP-dependent protein kin...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/10.1.225

    authors: Bartlomowicz B,Waxman DJ,Utesch D,Oesch F,Friedberg T

    更新日期:1989-01-01 00:00:00

  • Comparative benefits of Nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer.

    abstract::Gemcitabine has limited clinical benefits in pancreatic ductal adenocarcinoma. The solvent-based traditional taxanes docetaxel and paclitaxel have not shown clinical results superior to gemcitabine. Nab-paclitaxel, a water-soluble albumin-bound paclitaxel, may carry superior distribution properties into the tumor micr...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgt227

    authors: Awasthi N,Zhang C,Schwarz AM,Hinz S,Wang C,Williams NS,Schwarz MA,Schwarz RE

    更新日期:2013-10-01 00:00:00

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

    abstract::The androgen receptor (AR) is involved in the development and progression of prostate cancer. In order to find new compounds that may present novel mechanisms to attenuate the function of AR, we investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prost...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/22.3.409

    authors: Xing N,Chen Y,Mitchell SH,Young CY

    更新日期:2001-03-01 00:00:00

  • Association of chromosome 12p genetic polymorphisms with lung adenocarcinoma risk and prognosis.

    abstract::The mapping near Kras2 of pulmonary adenoma susceptibility 1 (Pas1), a major locus affecting inherited predisposition to lung cancer in mice prompted us to test the homologous human region (12p12) for association with lung adenocarcinoma, by a population-based study. We genotyped 213 lung adenocarcinoma patients and 2...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/18.10.1917

    authors: Manenti G,De Gregorio L,Pilotti S,Falvella FS,Incarbone M,Ravagnani F,Pierotti MA,Dragani TA

    更新日期:1997-10-01 00:00:00

  • Isoenzyme shift from glucokinase to hexokinase is not an early but a late event in hepatocarcinogenesis.

    abstract::The appearance of hepatocellular adenomas and carcinomas induced in rat liver with N-nitrosomorpholine is preceded by different types of preneoplastic foci consisting of phenotypically altered hepatocytes. The altered cells show changes in the activities of various enzymes including those of carbohydrate metabolism. G...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.9.1857

    authors: Klimek F,Bannasch P

    更新日期:1993-09-01 00:00:00

  • Src kinase is a direct target of apigenin against UVB-induced skin inflammation.

    abstract::Apigenin, a flavonoid abundant in various vegetables and fruits, including parsley and onions, has been reported to possess anticarcinogenic effects. However, the direct molecular target of apigenin and its chemopreventive effect on ultraviolet (UV)-induced skin inflammation are not understood fully. Herein, we examin...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs358

    authors: Byun S,Park J,Lee E,Lim S,Yu JG,Lee SJ,Chen H,Dong Z,Lee KW,Lee HJ

    更新日期:2013-02-01 00:00:00

  • Inhibition of cellular transformation by berry extracts.

    abstract::Recent studies have examined and demonstrated the potential cancer chemopreventive activity of freeze-dried berries including strawberries and black raspberries. Although ellagic acid, an abundant component in these berries, has been shown to inhibit carcinogenesis both in vivo and in vitro, several studies have repor...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/22.2.351

    authors: Xue H,Aziz RM,Sun N,Cassady JM,Kamendulis LM,Xu Y,Stoner GD,Klaunig JE

    更新日期:2001-02-01 00:00:00

  • Induction of free radicals and tumors in the kidneys of Wistar rats by ferric ethylenediamine-N,N'-diacetate.

    abstract::An iron chelate, ferric ethylenediamine-N,N'-diacetate [Fe(III)-EDDA], was found to produce hydroxyl radicals with hydrogen peroxide, as determined by both a deoxyribose degradation test and electron spin resonance. Hydroxyl radical production was inhibited not only by adding hydroxyl radical scavengers and catalase, ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.12.2817

    authors: Liu M,Okada S

    更新日期:1994-12-01 00:00:00

  • Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN.

    abstract::The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which contributes to tumorigenesis in many cancer types. While PTEN mutations occur in some melanomas, their precise mechanistic consequences have yet to be elucidated. We sought to identify novel downstream effectors of PI3K using a combinati...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgl016

    authors: Packer L,Pavey S,Parker A,Stark M,Johansson P,Clarke B,Pollock P,Ringner M,Hayward N

    更新日期:2006-09-01 00:00:00

  • Effects of green tea catechins in a rat multi-organ carcinogenesis model.

    abstract::The effects of dietary administration of green tea catechins (GTC) were examined using a multi-organ carcinogenesis model. Groups of 15 F344 male rats were initially treated with a single i.p. administration of 100 mg/kg body wt N-diethyl-nitrosamine, 4 i.p. administrations of 20 mg/kg body wt N-methylnitrosourea, 4 s...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.8.1549

    authors: Hirose M,Hoshiya T,Akagi K,Takahashi S,Hara Y,Ito N

    更新日期:1993-08-01 00:00:00

  • Genetic variants in selenoprotein genes increase risk of colorectal cancer.

    abstract::Low selenium (Se) status correlates with increased risk of colorectal cancer (CRC). Since Se exerts its biological roles through the selenoproteins, genetic variations in selenoprotein genes may influence susceptibility to CRC. This study analysed 12 single-nucleotide polymorphisms (SNPs) in selenoprotein genes [gluta...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgq076

    authors: Méplan C,Hughes DJ,Pardini B,Naccarati A,Soucek P,Vodickova L,Hlavatá I,Vrána D,Vodicka P,Hesketh JE

    更新日期:2010-06-01 00:00:00

  • Properties of the six isoforms of p63: p53-like regulation in response to genotoxic stress and cross talk with DeltaNp73.

    abstract::TP63, a member of the TP53 gene family, encodes two groups of three isoforms (alpha, beta and gamma). The TAp63 isoforms act as transcription factors. The DeltaNp63 isoforms lack the main transcription activation domain and act as dominant-negative inhibitors of transactivation (TA) isoforms. To clarify the role of th...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgm258

    authors: Petitjean A,Ruptier C,Tribollet V,Hautefeuille A,Chardon F,Cavard C,Puisieux A,Hainaut P,Caron de Fromentel C

    更新日期:2008-02-01 00:00:00

  • Influence of total dose and dose schedule on induction of urinary bladder cancer in the mouse by N-butyl-N-(4-hydroxybutyl)nitrosamine.

    abstract::Dose-response relationships in the induction of urinary bladder cancer in male C57BL/6 x DBA/2-F1 (BDF) mice by intragastric instillation of N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) were studied. Administration of a total dose of 0 to 80 mg OH-BBN in 10 weekly fractions to groups of 25 mice resulted in a linear ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/2.3.251

    authors: McCormick DL,Ronan SS,Becci PJ,Moon RC

    更新日期:1981-01-01 00:00:00

  • Bile acids do not form adducts when incubated with DNA in vitro.

    abstract::Bile acids have been implicated in the aetiology of colon cancer. We have previously found, using 32P-postlabelling, that bile from control patients and from patients with familial adenomatous polyposis (FAP) produces DNA adducts when incubated with salmon sperm DNA in vitro. In the present study we have incubated the...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.12.2945

    authors: Scates DK,Spigelman AD,Venitt S

    更新日期:1994-12-01 00:00:00

  • The induction of Ouar-mutations in nontransformable CVP3SC6 mouse fibroblasts.

    abstract::A line of C3H mouse fibroblasts designated CVP3SC6 (CVP) was found to be nonresponsive to the induction of morphological transformation by the polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) and its BaP-7,8-diol and BaP-diol-epoxide derivates. This cell line was, however, susceptible to BaP-induced mutation to ou...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.9.963

    authors: Gehly EB,Heidelberger C

    更新日期:1982-01-01 00:00:00