Inhibition of CXCR4/CXCL12 signaling axis by ursolic acid leads to suppression of metastasis in transgenic adenocarcinoma of mouse prostate model.

Abstract:

:Increasing evidences indicate that CXCR4/CXCL12 signaling pathway plays a pivotal role in the process of distant site metastasis that accounts for more than 90% of prostate cancer related deaths in patients. Thus, novel drugs that can downregulate CXCR4/CXCL12 axis have a great potential in the treatment of metastatic prostate cancer. In this report, we tested an agent, ursolic acid (UA) for its ability to modulate CXCR4 expression in prostate cancer cell lines and inhibit metastasis in vivo in transgenic adenocarcinoma of mouse prostate (TRAMP) model. We observed that UA downregulated the expression of CXCR4 in prostate cancer cells irrespective of their HER2 status in a dose- and time-dependent manner. Neither proteasome inhibitor nor lysosomal stabilization had any effect on UA-induced decrease in CXCR4 expression. When investigated for the molecular mechanisms, it was observed that the downregulation of CXCR4 was due to transcriptional regulation as indicated by downregulation of mRNA expression, inhibition of NF-κB activation and modulation of chromatin immunoprecipitation activity. Suppression of CXCR4 expression by UA further correlated with the inhibition of CXCL12-induced migration and invasion in prostate cancer cells. Finally, we also found that UA treatment can inhibit metastasis of prostate cancer to distal organs, including lung and liver and suppress CXCR4 expression levels in the prostate tissues of TRAMP mice. Overall, our experimental findings suggest that UA exerts its antimetastatic effects through the suppression of CXCR4 expression in prostate cancer both in vitro and in vivo.

journal_name

Int J Cancer

authors

Shanmugam MK,Manu KA,Ong TH,Ramachandran L,Surana R,Bist P,Lim LH,Kumar AP,Hui KM,Sethi G

doi

10.1002/ijc.26120

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

1552-63

issue

7

eissn

0020-7136

issn

1097-0215

journal_volume

129

pub_type

杂志文章
  • Control of endogenous cell regulators by the second-stage tumor promoter phorbol-12-retinoate 13-acetate.

    abstract::The phorbol esters phorbol 12-retinoate 13-acetate (RPA) and 12-O-tetradecanoyl phorbol 13-acetate (TPA) were used to investigate the role of tumor promoters in the control of hormone response in normal and leukemic myeloid cells. RPA and TPA inhibited the binding of [20-3H]phorbol 12,13-dibutyrate to the leukemic cel...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910310416

    authors: Simantov R,Marks F,Fürstenberger G,Sachs L

    更新日期:1983-04-15 00:00:00

  • Aberrant promoter methylation of p16(INK4a), RARB2 and SEMA3B in bronchial aspirates from patients with suspected lung cancer.

    abstract::Aberrant promoter methylation of normally unmethylated CpG-islands offers a promising tool for the development of molecular biomarkers. We investigated bronchial aspirates of patients admitted for suspected lung cancer with regard to the prevalence of aberrant methylation of potential marker genes. Applying quantitati...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21090

    authors: Grote HJ,Schmiemann V,Geddert H,Rohr UP,Kappes R,Gabbert HE,Böcking A

    更新日期:2005-09-20 00:00:00

  • Transplanted cultured cells from pregnancy-dependent mammary tumors have a heterogenous developmental potential.

    abstract::Cultured cells derived from pregnancy-dependent mouse mammary tumors (plaques) when transplanted into the gland-free mammary fat pad display a heterogeneous developmental potential. They not only gave rise to plaques but also produced normal mammary gland, hyperplastic alvoelar nodules (HAN), and autonomous mammary tu...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910230520

    authors: Aidells BD,Lee AE

    更新日期:1979-05-15 00:00:00

  • Fowlpox-based survivin vaccination for malignant mesothelioma therapy.

    abstract::Survivin protein is an attractive candidate for cancer immunotherapy since it is abundantly expressed in most common human cancers and mostly absent in normal adult tissues. Malignant mesothelioma (MM) is a deadly cancer associated with asbestos or erionite exposure for which no successful therapies are currently avai...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.28048

    authors: Bertino P,Panigada M,Soprana E,Bianchi V,Bertilaccio S,Sanvito F,Rose AH,Yang H,Gaudino G,Hoffmann PR,Siccardi A,Carbone M

    更新日期:2013-08-01 00:00:00

  • Comparisons of colon-cancer survival among European countries: The Eurocare Study.

    abstract::Under the aegis of EUROCARE, a European Union project to assemble survival data from population-based cancer registries and analyze them according to standardized procedures, we have investigated and compared colon-cancer survival in 10 European countries. We analyzed 68,283 colon-cancer cases diagnosed between 1978 a...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ijc.2910630109

    authors: Sant M,Capocaccia R,Verdecchia A,Gatta G,Micheli A,Mariotto A,Hakulinen T,Berrino F

    更新日期:1995-09-27 00:00:00

  • Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function.

    abstract::The human MUC1 gene expresses at least 2 type 1 membrane proteins: MUC1/REP, a polymorphic high m.w. MUC1 glycoprotein often highly expressed in breast cancer tissues and containing a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein, which lacks this repeat array and, therefore, is not poly...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19970529)71:5<741::aid-ijc

    authors: Baruch A,Hartmann M,Zrihan-Licht S,Greenstein S,Burstein M,Keydar I,Weiss M,Smorodinsky N,Wreschner DH

    更新日期:1997-05-29 00:00:00

  • A comparison of Epstein-Barr virus-specific T-cell immunity in malaria-endemic and -nonendemic regions of Papua New Guinea.

    abstract::Epstein-Barr virus genome-positive Burkitt's lymphoma is endemic in Africa and Papua New Guinea and in both countries the tumour is restricted to regions with holoendemic malaria. The present work has compared groups of healthy indigenous individuals living in malarious and non-malarious regions of Papua New Guinea fo...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910310609

    authors: Moss DJ,Burrows SR,Castelino DJ,Kane RG,Pope JH,Rickinson AB,Alpers MP,Heywood PF

    更新日期:1983-06-15 00:00:00

  • Measurement of a pancreatic cancer-associated antigen (DU-PAN-2) detected by a monoclonal antibody in sera of patients with digestive cancers.

    abstract::DU-PAN-2 is a high-molecular-weight glycoprotein defined by a murine monoclonal antibody (MAb) against a pancreatic ductal adenocarcinoma cell line. In order to evaluate the usefulness of this antigen as a tumor marker, we determined the serum level of the antigen by competitive inhibition radioimmunoassay in sera fro...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910370509

    authors: Sawabu N,Toya D,Takemori Y,Hattori N,Fukui M

    更新日期:1986-05-15 00:00:00

  • In vivo induction of endogenous retroviruses in BALB/c mouse hepatocytes by successive treatments with carbon tetrachloride and bromodeoxyuridine.

    abstract::The effects of bromodeoxyuridine (BrdUrd) incorporation into hepatocytes of carbon tetrachloride (CCl4)-induced regenerating liver of BALB/c mice on the induction of endogenous retroviruses was examined. From the nucliec acid hybridization studies, the maximum levels of hybridization were obtained for both N- and X-tr...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910240419

    authors: Ayukawa HM,Saltzburg D,Mukherjee BB

    更新日期:1979-10-15 00:00:00

  • Human discs large and scrib are localized at the same regions in colon mucosa and changes in their expression patterns are correlated with loss of tissue architecture during malignant progression.

    abstract::Loss of cell polarity is one of the hallmarks of malignant carcinomas. Most of the understanding about the link between cell polarity and proliferation control comes from studies on the Drosophila tumor suppressors discs large (Dlg), scribble (Scrib) and lethal giant larvae (lgl). Mammalian homologues of these protein...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21982

    authors: Gardiol D,Zacchi A,Petrera F,Stanta G,Banks L

    更新日期:2006-09-15 00:00:00

  • The bidirectional interaction of the gut microbiome and the innate immune system: Implications for chemotherapy-induced gastrointestinal toxicity.

    abstract::Chemotherapy-induced gastrointestinal toxicity (CIGT) occurs in up to 80% of all patients undergoing cancer treatment, and leads to symptoms such as diarrhoea, abdominal bleeding and pain. There is currently limited understanding of how to predict an individual patient's risk of CIGT. It is believed the gut microbiome...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/ijc.31836

    authors: Secombe KR,Coller JK,Gibson RJ,Wardill HR,Bowen JM

    更新日期:2019-05-15 00:00:00

  • The evolving epidemic of breast cancer in sub-Saharan Africa: Results from the African Cancer Registry Network.

    abstract::Breast cancer (BC) is the leading cause of cancer in sub-Saharan Africa (SSA) with rapidly increasing incidence rates reported in Uganda and Zimbabwe. However, the magnitude of these rising trends in premenopausal and postmenopausal women is unknown in most African countries. We used data from the African Cancer Regis...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.33014

    authors: Joko-Fru WY,Jedy-Agba E,Korir A,Ogunbiyi O,Dzamalala CP,Chokunonga E,Wabinga H,Manraj S,Finesse A,Somdyala N,Liu B,McGale P,Jemal A,Bray F,Parkin DM

    更新日期:2020-10-15 00:00:00

  • Novel approach for detecting global epigenetic alterations associated with tumor cell aneuploidy.

    abstract::Although aneuploidy is commonly observed in human cancers, the molecular mechanism underlying aneuploidization remains unclear. We used multiploid cancer model that had diploid and aneuploid cancer cells within the same cancerous tissue and attempted to detect specific epigenetic alterations associated with tumor cell...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22847

    authors: Habano W,Sugai T,Jiao YF,Nakamura S

    更新日期:2007-10-01 00:00:00

  • Effects of the farnesyltransferase inhibitor UCF-1C/manumycin on growth and p21-ras post-translational processing in NIH3T3 cells.

    abstract::Examination of the effect of the farnesylprotein transferase (FPTase) inhibitor UCF1-C/manumycin on NIH3T3 cells transfected with a normal N-ras gene and expressing high levels of the corresponding p21-ras protein showed that 10 microm UCF1-C immediately and reversibly inhibited growth in these cells, without modifyin...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19980518)76:4<601::aid-ijc

    authors: Servais P,Gulbis B,Fokan D,Galand P

    更新日期:1998-05-18 00:00:00

  • Malignant lymphoma of the central nervous system in Japan: histologic and immunohistologic studies.

    abstract::Ninety-seven Japanese patients with so-called primary non-Hodgkin's lymphoma of the central nervous system (CNS-NHL), unrelated to the acquired immunodeficiency syndrome (AIDS) or organ transplantation, were reviewed. The patients' ages ranged from 1 to 87 years (median: 58 years) with a male to female ratio of 1.77:1...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910450410

    authors: Aozasa K,Ohsawa M,Yamabe H,Shima N,Kirimoto K,Yamane T,Tsujimoto M,Kobayashi Y,Kurata A,Osada H

    更新日期:1990-04-15 00:00:00

  • A prospective study of adiposity and postmenopausal breast cancer risk: the Malmö Diet and Cancer Study.

    abstract::High BMI is a well-known risk factor for postmenopausal breast cancer. There have been some reports of excess risk in association with weight gain and WHR, but little is known about the influence of body fatness per se. Using data from the Malmö Diet and Cancer Study, a prospective cohort study, 12,159 postmenopausal ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10799

    authors: Lahmann PH,Lissner L,Gullberg B,Olsson H,Berglund G

    更新日期:2003-01-10 00:00:00

  • Genetic variation of XPA gene and risk of cancer: a systematic review and pooled analysis.

    abstract::XPA, a zinc-finger DNA-binding protein, play an important role in both global genome and transcription-coupled repair pathways. XPA -4G>A polymorphism was identified in the 5' noncoding region, located four nucleotides upstream of the ATG start codon. Previous studies have shown that this polymorphism may affect mRNA ...

    journal_title:International journal of cancer

    pub_type: 杂志文章,meta分析,评审

    doi:10.1002/ijc.26391

    authors: Ding D,Zhang Y,Yu H,Guo Y,Jiang L,He X,Ma W,Zheng W

    更新日期:2012-07-15 00:00:00

  • Targeted imaging of breast tumor progression and therapeutic response in a human uMUC-1 expressing transgenic mouse model.

    abstract::The ability to monitor breast cancer initiation and progression on the molecular level would provide an effective tool for early diagnosis and therapy. In the present study, we focused on the underglycosylated MUC-1 tumor antigen (uMUC-1), which is directly linked to tumor progression from pre-malignancy to advanced m...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.27872

    authors: Ghosh SK,Uchida M,Yoo B,Ross AW,Gendler SJ,Gong J,Moore A,Medarova Z

    更新日期:2013-04-15 00:00:00

  • CDKN2a mutation-negative melanoma families have increased risk exclusively for skin cancers but not for other malignancies.

    abstract::Germline CDKN2A mutations are found in 5-20% of melanoma families. Numerous studies have shown that carriers of CDKN2A mutations have increased risks of non-melanoma cancers, but so far there have been no studies investigating cancer risks in CDKN2A wild type (wt) melanoma families. In this prospective cohort study, i...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29595

    authors: Helgadottir H,Höiom V,Tuominen R,Jönsson G,Månsson-Brahme E,Olsson H,Hansson J

    更新日期:2015-11-01 00:00:00

  • Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by a FokI variant supports a chemoprotective action of Vitamin D intake mediated through VDR binding.

    abstract::Vitamin D has anticarcinogenic properties and might influence colorectal cancer (CRC) risk, but the epidemiological evidence is inconsistent. Many mechanisms of action for vitamin D have been proposed, with some of them initiating via its binding to the vitamin D receptor (VDR). Using a large Scottish case-control stu...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23769

    authors: Theodoratou E,Farrington SM,Tenesa A,McNeill G,Cetnarskyj R,Barnetson RA,Porteous ME,Dunlop MG,Campbell H

    更新日期:2008-11-01 00:00:00

  • Endoscopic screening for synchronous esophageal neoplasia among patients with incident head and neck cancer: Prevalence, risk factors, and outcomes.

    abstract::Esophageal squamous-cell neoplasia (ESCN) is a common second primary neoplasia found in patients with head-and-neck squamous-cell carcinoma (HNSCC). This study sought to identify the risk factors for synchronous ESCN and how they influence survival in HNSCC patient. Eight hundred and fifteen incident HNSCC patients we...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.30911

    authors: Wang YK,Chuang YS,Wu TS,Lee KW,Wu CW,Wang HC,Kuo CT,Lee CH,Kuo WR,Chen CH,Wu DC,Wu IC

    更新日期:2017-11-15 00:00:00

  • Mutant allele-specific imbalance modulates prognostic impact of KRAS mutations in colorectal adenocarcinoma and is associated with worse overall survival.

    abstract::The prognostic impact of distinct KRAS mutations in colorectal carcinomas is not fully characterized. We hypothesized that the prognostic impact of KRAS mutations is modulated by KRAS mutant allele-specific imbalance (MASI). KRAS MASI was assessed by sequencing electropherograms in KRAS-mutated colorectal carcinomas (...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.27461

    authors: Hartman DJ,Davison JM,Foxwell TJ,Nikiforova MN,Chiosea SI

    更新日期:2012-10-15 00:00:00

  • Estrogenic and anti-estrogenic regulation of estrogen receptor in MCF-7 breast-cancer cells: comparison of immunocytochemical data with biochemical measurements.

    abstract::Data from immunocytochemical assessment of estrogen receptor (ER) regulation in MCF-7 cells under estrogenic and anti-estrogenic stimulation were compared with those obtained by enzyme immunoassay (Abbott ER-EIA). Similar trends were observed, although ER level variations were less marked when assessed immunocytochemi...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19981209)78:6<760::aid-ijc

    authors: Seo HS,Larsimont D,Querton G,El Khissiin A,Laios I,Legros N,Leclercq G

    更新日期:1998-12-09 00:00:00

  • Quantitative association between body mass index and the risk of cancer: A global Meta-analysis of prospective cohort studies.

    abstract::Numerous studies have suggested that excess body weight is associated with increased cancer risk. To examine this putative association, we performed a systematic review and quantitative meta-analysis of cohort studies reporting body mass index (BMI) and the risk of 23 cancer types. PubMed, Embase, and Web of Science w...

    journal_title:International journal of cancer

    pub_type: 杂志文章,meta分析

    doi:10.1002/ijc.31553

    authors: Fang X,Wei J,He X,Lian J,Han D,An P,Zhou T,Liu S,Wang F,Min J

    更新日期:2018-10-01 00:00:00

  • Farnesyl thiosalicylic acid inhibits the growth of melanoma cells through a combination of cytostatic and pro-apoptotic effects.

    abstract::Novel classes of drug that interfere with the signalling of the small G-protein Ras, the so-called Ras antagonists, are showing much promise as novel anti-cancer agents. In this study, we demonstrate that the novel Ras antagonist farnesylthiosalicylic acid (FTS) inhibits the growth of Colo 853 melanoma cells through a...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10213

    authors: Smalley KS,Eisen TG

    更新日期:2002-04-01 00:00:00

  • Development of an intrinsic P-glycoprotein-mediated doxorubicin resistance in quiescent cell layers of large, multicellular prostate tumor spheroids.

    abstract::Growing multicellular prostate tumor spheroids develop quiescent cell subpopulations in central regions with features of intrinsic multicell-mediated drug resistance. Doxorubicin (dox) uptake was significantly reduced in large spheroids (diameter 400+/-70 microm), which consist predominantly of quiescent cells, as com...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19980316)75:6<855::aid-ijc

    authors: Wartenberg M,Frey C,Diedershagen H,Ritgen J,Hescheler J,Sauer H

    更新日期:1998-03-16 00:00:00

  • Epigenetic silencing of maspin gene expression in human breast cancers.

    abstract::Maspin is a tumor suppressor whose expression is lost in many advanced breast cancers. Maspin has been shown to inhibit cell motility, invasion and metastasis; however, its precise role in normal mammary epithelium remains to be elucidated. Although expression of maspin mRNA is low or absent in most human breast cance...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(20000315)85:6<805::aid-ijc

    authors: Domann FE,Rice JC,Hendrix MJ,Futscher BW

    更新日期:2000-03-15 00:00:00

  • Prescription drug use and risk of acute myeloid leukemia by French-American-British subtype: results from a Los Angeles County case-control study.

    abstract::Chemotherapy is a well-established risk factor for acute myeloid leukemia (AML) but little is known about other prescription drugs and AML risk. We report data from a population-based Los Angeles County study in which 299 matched case-control pairs had complete data on prescription drug use and 88% of cases were subty...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20788

    authors: Pogoda JM,Katz J,McKean-Cowdin R,Nichols PW,Ross RK,Preston-Martin S

    更新日期:2005-04-20 00:00:00

  • Transcriptional variations in the wider peritumoral tissue environment of pancreatic cancer.

    abstract::Transcriptional profiling was performed on 452 RNA preparations isolated from various types of pancreatic tissue from tumour patients and healthy donors, with a particular focus on peritumoral samples. Pancreatic ductal adenocarcinomas (PDAC) and cystic tumours were most different in these non-tumorous tissues surroun...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31087

    authors: Bauer AS,Nazarov PV,Giese NA,Beghelli S,Heller A,Greenhalf W,Costello E,Muller A,Bier M,Strobel O,Hackert T,Vallar L,Scarpa A,Büchler MW,Neoptolemos JP,Kreis S,Hoheisel JD

    更新日期:2018-03-01 00:00:00

  • Defining a role for Sonic hedgehog pathway activation in desmoplastic medulloblastoma by identifying GLI1 target genes.

    abstract::A subgroup of medulloblastomas shows constitutive activation of the Sonic hedgehog pathway with expression of GLI1. We identified the subset of GLI1 transforming target genes specifically expressed in medulloblastomas by comparing GLI1 targets in RK3E cells transformed by GLI1 with the gene expression profile of Sonic...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23929

    authors: Yoon JW,Gilbertson R,Iannaccone S,Iannaccone P,Walterhouse D

    更新日期:2009-01-01 00:00:00