Inhibition of hyaluronan synthesis in breast cancer cells by 4-methylumbelliferone suppresses tumorigenicity in vitro and metastatic lesions of bone in vivo.

Abstract:

:Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Previous studies demonstrated that inhibition of HA suppressed the tumorigenicity of various malignant tumors including breast cancer. 4-methylumbelliferone (MU) has been reported to inhibit HA synthesis in several cell types. However, few studies have focused on the effects of HA inhibition in breast cancer cells by MU, nor the effects on bone metastasis. We hypothesized that MU would suppress the progression of bone metastasis via inhibition of HA synthesis. Here, we investigated the effects of MU on HA expression in MDA-MB-231 breast cancer cell line in addition to their tumorigenicity in vitro and in vivo. HAS2 mRNA expression was downregulated after 6 and 24 hr treatment with MU. Quantitative analysis of HA revealed that MU significantly inhibited the intracellular and cell surface HA. MU significantly inhibited cell growth and induced apoptosis as determined by cell proliferation and TUNEL assays, respectively. Phosphorylation of Akt was suppressed after 12 and 24 hr treatment with MU. MU treatment also inhibited cell motility as well as cell invasiveness. MU also inhibited cell growth and motility in murine fibroblast cell line NIH3T3. In vivo, administration of MU inhibited the expansion of osteolytic lesions on soft X-rays in mouse breast cancer xenograft models. HA accumulation in bone metastatic lesions was perturbed peripherally. These data suggest that MU might be a therapeutic candidate for bone metastasis of breast cancer via suppression of HA synthesis and accumulation.

journal_name

Int J Cancer

authors

Urakawa H,Nishida Y,Wasa J,Arai E,Zhuo L,Kimata K,Kozawa E,Futamura N,Ishiguro N

doi

10.1002/ijc.26014

subject

Has Abstract

pub_date

2012-01-15 00:00:00

pages

454-66

issue

2

eissn

0020-7136

issn

1097-0215

journal_volume

130

pub_type

杂志文章
  • Clinical and biological significance of HSP89 alpha in human breast cancer.

    abstract::In order to isolate and characterize genes whose expression may be altered in breast malignancy, we screened a cDNA library with a polyclonal anti-serum against breast-cancer-metastasis membranes and isolated several immunopositive clones. One of these, AJ1, was analyzed in detail and found to be expressed at varying ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910500315

    authors: Jameel A,Skilton RA,Campbell TA,Chander SK,Coombes RC,Luqmani YA

    更新日期:1992-02-01 00:00:00

  • Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases.

    abstract::A human cancer vaccine composed of autologous tumor cells modified with the hapten dinitrofluorobenzene (DNP) induces cell-mediated immunity to the tumor cells and the development of inflammatory responses within metastatic sites. In this study we determined whether DNP vaccine could induce regression of established m...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.1506.abs

    authors: Berd D,Sato T,Cohn H,Maguire HC Jr,Mastrangelo MJ

    更新日期:2001-11-01 00:00:00

  • Expression, subcellular localization and putative function of platelet-type 12-lipoxygenase in human prostate cancer cell lines of different metastatic potential.

    abstract::The involvement of 12-lipoxygenase (12-LOX) expression and function in tumor metastasis has been demonstrated in several murine tumor cell lines. In addition, 12-LOX expression was detected in human prostatic tumors and correlated to the clinical stage of disease. Here we provide data that human prostate cancer cell l...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(20000701)87:1<37::aid-ijc6>3.0.c

    authors: Timár J,Rásó E,Döme B,Li L,Grignon D,Nie D,Honn KV,Hagmann W

    更新日期:2000-07-01 00:00:00

  • Induction of tubulin by docetaxel is associated with p53 status in human non small cell lung cancer cell lines.

    abstract::Docetaxel (DOC), a member of the taxane family of anticancer drugs, binds to tubulin and produces unnaturally stable microtubules that induce cell death. DOC is used clinically alone or in combination with other compounds to treat advanced stages of cancer. We have treated the human lung cancer cell lines A549 and H12...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21372

    authors: Chang JT,Chang GC,Ko JL,Liao HY,Liu HJ,Chen CC,Su JM,Lee H,Sheu GT

    更新日期:2006-01-15 00:00:00

  • DHPLC is superior to SSCP in screening p53 mutations in esophageal cancer tissues.

    abstract::Mutations of the p53 tumor-suppressor gene universally occur on exons 5-8 in human cancer. We analyzed these mutations in esophageal cancer tissue from 207 patients in China using 2 methods, single-strand conformation polymorphism (SSCP), one of the most frequently used methods, and the recently developed denaturing h...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20712

    authors: Yamanoshita O,Kubota T,Hou J,Ping YM,Zhang XL,Li XP,Li SS,Li XX,Zhu DC,Fukushima Y,Nakajima T

    更新日期:2005-03-10 00:00:00

  • Anti-retrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in vivo increases when it is less frequently administered.

    abstract::Different treatment schedules have been investigated when evaluating the inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and 3'-azido-2',3'-dideoxythymidine (AZT) on the replication of human immunodeficiency virus type I (HIV-I) in MT-4 cells, transformation of C3H/3T3 cells by Moloney murine sarcoma v...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910460233

    authors: Balzarini J,Naesens L,De Clercq E

    更新日期:1990-08-15 00:00:00

  • Quantitative analysis of survivin mRNA expression in urine and tumor tissue of bladder cancer patients and its potential relevance for disease detection and prognosis.

    abstract::Suppression of apoptosis may favor the onset and progression of cancer. Survivin is an inhibitor of apoptosis that has been suggested as a novel diagnostic/prognostic marker of bladder cancer. In this study, survivin mRNA expression was measured by a sensitive real-time PCR assay in tumor tissue and urine from bladder...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21000

    authors: Weikert S,Christoph F,Schrader M,Krause H,Miller K,Müller M

    更新日期:2005-08-10 00:00:00

  • Prevalence of antibodies to human papillomaviruses in the general population of the Czech Republic.

    abstract::Sera from 450 individuals between the age of 1 and 80 years, representing the general population of the Czech Republic, were tested for the presence of antibodies to human-papillomavirus(HPV)-derived antigens. The following antigens were used: (i) HPV1 virions; (ii) HPV16, -18 and -33-virus-like particles (VLP); (iii)...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19980831)77:5<689::aid-ijc

    authors: Hamsíková E,Ludvíková V,Smahel M,Sapp M,Vonka V

    更新日期:1998-08-31 00:00:00

  • Variations in sex hormone metabolism genes, postmenopausal hormone therapy and risk of endometrial cancer.

    abstract::We investigated whether variants in sex steroid hormone metabolism genes modify the effect of hormone therapy (HT) on endometrial cancer risk in postmenopausal non-Hispanic white women. A nested case-control study was conducted within the California Teachers Study (CTS). We genotyped htSNPs in six genes involved in th...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.26163

    authors: Razavi P,Lee E,Bernstein L,Van Den Berg D,Horn-Ross PL,Ursin G

    更新日期:2012-04-01 00:00:00

  • Multiple births and risk of breast cancer.

    abstract::Data from a large, multicenter, population-based case-control study were analyzed to investigate the relation between multiple birth pregnancies and subsequent breast-cancer risk in the gravidas. Women less than 75 years old who had breast cancer were identified from statewide tumor registries in Wisconsin, western Ma...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/ijc.2910620209

    authors: Dietz AT,Newcomb PA,Storer BE,Longnecker MP,Mittendorf R

    更新日期:1995-07-17 00:00:00

  • Carcinogenic potential of hycanthone in mice and hamsters.

    abstract::Hycanthone was administered to Schistosoma mansoni-infected and non-infected Syrian golden hamsters and Swiss mice by intraperitoneal and intramuscular injection of amounts up to the maximum tolerated dose. No tumors attributable to treatment were observed in hamsters. In infected mice, the overall incidence of hepato...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910230117

    authors: Bulay O,Urman H,Patil K,Clayson DB,Shubik P

    更新日期:1979-01-15 00:00:00

  • DESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma.

    abstract::Esophageal cancer is ranked as the eighth most common cancer and the sixth leading cause of cancer deaths worldwide. To identify candidate tumor suppressor genes related to esophageal squamous cell carcinoma (ESCC) development, a cDNA microarray analysis was performed using paired tumor and nontumor tissue samples fro...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.30034

    authors: Ng HY,Ko JM,Yu VZ,Ip JC,Dai W,Cal S,Lung ML

    更新日期:2016-06-15 00:00:00

  • Genes and molecular pathways related to radioresistance of oral squamous cell carcinoma cells.

    abstract::To identify genes associated with radioresistant oral squamous cell carcinoma (OSCC), we compared gene expression signatures between OSCC cell lines exhibiting radioresistance and cells with radiosensitivity after X-ray irradiation in a dose-dependent manner using Affymetrix GeneChip analysis with Human Genome-U133 pl...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22561

    authors: Ishigami T,Uzawa K,Higo M,Nomura H,Saito K,Kato Y,Nakashima D,Shiiba M,Bukawa H,Yokoe H,Kawata T,Ito H,Tanzawa H

    更新日期:2007-05-15 00:00:00

  • Enhanced killing of therapy-induced senescent tumor cells by oncolytic measles vaccine viruses.

    abstract::Therapy-induced senescence (TIS) as a permanent growth arrest can be induced by various stimuli, including anticancer compounds. TIS emerged as a promising strategy to overcome resistance phenomena. However, senescent cancer cells might regain proliferation activity in vivo or even secrete tumor-promoting cytokines. T...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.28350

    authors: Weiland T,Lampe J,Essmann F,Venturelli S,Berger A,Bossow S,Berchtold S,Schulze-Osthoff K,Lauer UM,Bitzer M

    更新日期:2014-01-01 00:00:00

  • Evidence of benefit from centralised treatment of ovarian cancer: a nationwide population-based survival analysis in Finland.

    abstract::To assess the effect of different hospital types or surgical volume on the survival of ovarian cancer patients, a nationwide and population-based analysis was carried out in Finland. The study included all 3,851 ovarian cancer patients operated from 1983-94. The patients were classified according to the hospital of th...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10754

    authors: Kumpulainen S,Grénman S,Kyyrönen P,Pukkala E,Sankila R

    更新日期:2002-12-10 00:00:00

  • Frequent allelic changes at chromosome 7q34 but lack of mutation of the BRAF in papillary renal cell tumors.

    abstract::We have analyzed the BRAF locus on chromosome 7q34 with microsatellites for allelic changes and exons 11 and 15 of the BRAF with sequencing for mutations in 50 kidney cancers including 20 papillary, 15 conventional and 15 chromophobe renal cell carcinomas (RCC). Allelic changes at the BRAF locus were seen in 16 of the...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.11305

    authors: Nagy A,Balint I,Kovacs G

    更新日期:2003-10-10 00:00:00

  • Adoptive transfer of human natural killer cells in mice with severe combined immunodeficiency inhibits growth of Hsp70-expressing tumors.

    abstract::In vitro, tumor-selective Hsp70 plasma membrane localization correlates with increased sensitivity to lysis mediated by a subpopulation of human natural killer (NK) cells that adhere to plastic following cytokine stimulation. In the present study, we analyzed the capacity of adoptively transferred human NK cells in SC...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(20001201)88:5<791::aid-ijc17>3.0

    authors: Multhoff G,Pfister K,Botzler C,Jordan A,Scholz R,Schmetzer H,Burgstahler R,Hiddemann W

    更新日期:2000-12-01 00:00:00

  • Cancer incidence in a cohort of Ontario and Quebec women having bilateral breast augmentation.

    abstract::The possibility that women, who receive breast implants for cosmetic purposes, have increased long-term risks of developing cancer continues to be debated. The objective of our study was to prospectively examine cancer incidence among women who received breast implants. A cohort was assembled of 24,558 women, 18 years...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21711

    authors: Brisson J,Holowaty EJ,Villeneuve PJ,Xie L,Ugnat AM,Latulippe L,Mao Y

    更新日期:2006-06-01 00:00:00

  • Transactivation of the CCL5/RANTES gene by Epstein-Barr virus latent membrane protein 1.

    abstract::Chemokines and chemokine receptors mediate lymphocyte migration and tissue localization. To analyze CCL5 (RANTES) expression by EBV-infected cells, we examined the expression of CCL5 in BL cell lines. Among 4 BL cell lines, those infected with EBV selectively expressed the CCL5 gene and secreted CCL5. Four cell lines ...

    journal_title:International journal of cancer

    pub_type: 杂志文章,收录出版

    doi:10.1002/ijc.20784

    authors: Uchihara JN,Krensky AM,Matsuda T,Kawakami H,Okudaira T,Masuda M,Ohta T,Takasu N,Mori N

    更新日期:2005-05-01 00:00:00

  • Tumoricidal activity of high-dose tumor necrosis factor-alpha is mediated by macrophage-derived nitric oxide burst and permanent blood flow shutdown.

    abstract::This study investigates the role of tumor nitric oxide (NO) and vascular regulation in tumor ulceration following high-dose tumor necrosis factor-alpha (TNF) treatment. Using TNF-responsive (MethA) and nonresponsive (LL2) mouse tumors, tumor NO concentration was measured with an electrochemical sensor and tumor blood ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23499

    authors: Menon C,Bauer TW,Kelley ST,Raz DJ,Bleier JI,Patel K,Steele K,Prabakaran I,Shifrin A,Buerk DG,Sehgal CM,Fraker DL

    更新日期:2008-07-15 00:00:00

  • Over-expression and amplification of the c-myc gene in human urothelial carcinoma.

    abstract::To understand the mechanisms underlying increased expression of Myc protein in human urinary bladder cancer, expression of c-myc mRNA and the copy number of the c-myc gene were determined. Expression of mRNA was measured by quantitative RT-PCR in 40 urothelial carcinomas and in 18 histologically normal mucosae. Mean e...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19990420)84:2<169::aid-ijc

    authors: Christoph F,Schmidt B,Schmitz-Dräger BJ,Schulz WA

    更新日期:1999-04-20 00:00:00

  • A dietary pattern based on estrogen metabolism is associated with breast cancer risk in a prospective cohort of postmenopausal women.

    abstract::Increased exposure to estrogen is a risk factor for postmenopausal breast cancer, and dietary factors can influence estrogen metabolism. However, studies of diet and breast cancer have been inconclusive. We developed a dietary pattern associated with levels of unconjugated estradiol and the ratio of 2- and 16-hydroxyl...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31387

    authors: Guinter MA,McLain AC,Merchant AT,Sandler DP,Steck SE

    更新日期:2018-08-01 00:00:00

  • Pronounced antitumor efficacy of doxorubicin when given as the prodrug DOX-GA3 in combination with a monoclonal antibody beta-glucuronidase conjugate.

    abstract::A glucuronide doxorubicin prodrug N-[4-doxorubicin-N-carbonyl (oxymethyl) phenyl] O-beta-glucuronyl carbamate (DOX-GA3) has been developed to improve the antitumor effects of doxorubicin (DOX). The prodrug was originally designed to be activated into drug by human beta-glucuronidase (GUS) released from tumor cells in ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(200002)9999:9999<::aid-ijc1075>3

    authors: Houba PH,Boven E,van der Meulen-Muileman IH,Leenders RG,Scheeren JW,Pinedo HM,Haisma HJ

    更新日期:2001-02-15 00:00:00

  • Claudin7-dependent exosome-promoted reprogramming of nonmetastasizing tumor cells.

    abstract::Claudin7 (cld7) is a cancer-initiating cell (CIC) marker in gastrointestinal tumors, a cld7-knockdown (kd) being accompanied by loss of tumor progression. Tumor exosomes (TEX) restoring CIC activities, we explored the contribution of cld7. This became particularly interesting, as tight junction (TJ)- and glycolipid-en...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32312

    authors: Kyuno D,Zhao K,Schnölzer M,Provaznik J,Hackert T,Zöller M

    更新日期:2019-10-15 00:00:00

  • Cervical nitric oxide release and persistence of high-risk human papillomavirus in women.

    abstract::Nitric oxide may serve as one cofactor for human papillomavirus (HPV)-induced development of cervical cancer. Therefore, we first assessed the levels of cervical fluid nitric oxide metabolite (NOx) in 283 women with and without high-risk (hr) HPV. The NOx level in women with hr HPV (48.4 μmol/L [95% CI: 39.4-56.6], n ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25637

    authors: Rahkola P,Väisänen-Tommiska M,Tuomikoski P,Ylikorkala O,Mikkola TS

    更新日期:2011-06-15 00:00:00

  • Efficient tumor targeting by single-domain antibody fragments of camels.

    abstract::The variable domain of functional heavy chain antibodies (VHH) devoid of light chains, found in camels, constitute the smallest intact antigen-binding domain fragment. Two camel single-domain fragments, cAb-Lys2 and cAb-Lys3, recognizing an overlapping epitope of lysozyme with a dissociation constant of 2 nM and 65 nM...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10212

    authors: Cortez-Retamozo V,Lauwereys M,Hassanzadeh Gh G,Gobert M,Conrath K,Muyldermans S,De Baetselier P,Revets H

    更新日期:2002-03-20 00:00:00

  • Human papillomavirus-16 DNA methylation patterns support a causal association of the virus with oral squamous cell carcinomas.

    abstract::Infection with human papillomavirus-16 (HPV-16) is the cause of most anogenital carcinomas. This virus is also detected in about 20% of all head and neck squamous cell carcinomas. While there is strong evidence for a causal etiological role in the case of tonsillar carcinomas, causal association with malignant lesions...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22563

    authors: Balderas-Loaeza A,Anaya-Saavedra G,Ramirez-Amador VA,Guido-Jimenez MC,Kalantari M,Calleja-Macias IE,Bernard HU,Garcia-Carranca A

    更新日期:2007-05-15 00:00:00

  • Serum concentrations of squamous cell carcinoma antigen in patients with vulvar intraepithelial neoplasia and vulvar cancer.

    abstract::Our aim was to evaluate whether serum concentrations of squamous cell carcinoma antigen (SCC-Ag) are an independent prognostic factor in patients with vulvar cancer. We measured SCC-Ag in pretreatment serum samples of 55 patients with squamous cell vulvar cancer, 30 patients with vulvar intraepithelial neoplasia (VIN)...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19990621)84:3<299::aid-ijc

    authors: Hefler L,Obermair A,Tempfer C,van Houte M,Maenner G,Reinthaller A,Leodolter S,Kainz C

    更新日期:1999-06-21 00:00:00

  • Tumor heterogeneity and cancer stem cell paradigm: updates in concept, controversies and clinical relevance.

    abstract::Although tumor heterogeneity is widely accepted, the existence of cancer stem cells (CSCs) and their proposed role in tumor maintenance has always been challenged and remains a matter of debate. Recently, a path-breaking chapter was added to this saga when three independent groups reported the in vivo existence of CSC...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审

    doi:10.1002/ijc.28804

    authors: Singh AK,Arya RK,Maheshwari S,Singh A,Meena S,Pandey P,Dormond O,Datta D

    更新日期:2015-05-01 00:00:00

  • Phase I clinical trial of adoptive transfer of expanded natural killer cells in combination with IgG1 antibody in patients with gastric or colorectal cancer.

    abstract::Natural killer (NK) cells exhibit strong cytotoxic activity against tumor cells without prior sensitization, and have the potential to exert antibody-dependent cellular cytotoxicity (ADCC). In this clinical trial, we examined the safety and efficacy of the use of NK cells, generated using a novel expansion system, in ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31285

    authors: Ishikawa T,Okayama T,Sakamoto N,Ideno M,Oka K,Enoki T,Mineno J,Yoshida N,Katada K,Kamada K,Uchiyama K,Handa O,Takagi T,Konishi H,Kokura S,Uno K,Naito Y,Itoh Y

    更新日期:2018-06-15 00:00:00