Sphingosine kinase 2 deficient tumor xenografts show impaired growth and fail to polarize macrophages towards an anti-inflammatory phenotype.

Abstract:

:A challenging task of the immune system is to fight cancer cells. However, a variety of human cancers educate immune cells to become tumor supportive. This is exemplified for tumor-associated macrophages (TAMs), which are polarized towards an anti-inflammatory and cancer promoting phenotype. Mechanistic explanations, how cancer cells influence the macrophage phenotype are urgently needed to address potential anti-cancer strategies along this line. One potential immune modulating compound, sphingosine-1-phosphate (S1P), was recently highlighted in both tumor growth and immune modulation. Using a xenograft model in nude mice, we demonstrate a supportive role of sphingosine kinase 2 (SphK2), one of the S1P-producing enzymes for tumor progression. The growth of SphK2-deficient MCF-7 breast tumor xenografts was markedly delayed when compared with controls. Infiltration of macrophages in SphK2-deficient and control tumors was comparable. However, TAMs from SphK2-deficient tumors displayed a pronounced anti-tumor phenotype, showing an increased expression of pro-inflammatory markers/mediators such as NO, TNF-alpha, IL-12 and MHCII and a low expression of anti-inflammatory IL-10 and CD206. These data suggest a role for S1P, generated by SphK2, in early tumor development by affecting macrophage polarization.

journal_name

Int J Cancer

authors

Weigert A,Schiffmann S,Sekar D,Ley S,Menrad H,Werno C,Grosch S,Geisslinger G,Brüne B

doi

10.1002/ijc.24594

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

2114-21

issue

9

eissn

0020-7136

issn

1097-0215

journal_volume

125

pub_type

杂志文章
  • Evidence of involvement of CD44 in endothelial cell proliferation, migration and angiogenesis in vitro.

    abstract::Angiogenesis is essential for tumor growth and metastasis. In the process of angiogenesis, the interaction between adhesive proteins of endothelial cells and extracellular matrix components plays an important role by mediating cell attachment, which is indispensable for their motility, and by transmitting the regulato...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0215(19960529)66:5<664::AID-IJC

    authors: Trochon V,Mabilat C,Bertrand P,Legrand Y,Smadja-Joffe F,Soria C,Delpech B,Lu H

    更新日期:1996-05-29 00:00:00

  • Lymphocyte stimulation by autologous tumor cells in the presence of serum from the same patient or from healthy donors.

    abstract::Lymphocyte blastogenesis induced by autologous tumor biopsy cells, by allogeneic lymphocytes and by PHA, was performed in the presence of autologous or allogeneic serum collected from normal blood donors. In 13 of the 15 cases lymphocyte stimulation by autologous tumor cells was inhibited in the presence of autologous...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910160517

    authors: Vánky F,Klein E,Stjernswärd J,Trempe G

    更新日期:1975-11-15 00:00:00

  • Monoclonal antibody against a naturally occurring rat mammary carcinoma.

    abstract::Inbred rats were hyper-immunised against a syngeneic transplanted mammary carcinoma, Sp4, which originally arose spontaneously in a breeding female. Spleen cells from Sp4-immune rats were fused with P3-NSI-Ag4 mouse myeloma cells, and supernatants from the hybrid progeny were screened for antibody reacting with Sp4 ce...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910260311

    authors: Gunn B,Embleton MJ,Middle JG,Baldwin RW

    更新日期:1980-09-15 00:00:00

  • Urine estrogens and breast cancer risk factors among post-menopausal women.

    abstract::Creatinine-adjusted levels of estrone, estradiol and estriol were determined in overnight urine specimens from 220 post-menopausal women, aged 54 to 66 years, from Boston (121 women) and Athens (99 women). The associations of individual and total estrogens with various characteristics of the women (age at menopause, y...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910400602

    authors: Trichopoulos D,Brown J,MacMahon B

    更新日期:1987-12-15 00:00:00

  • Prevalence and clinical impact of TP53 germline mutations in Chinese women with breast cancer.

    abstract::The prevalence and clinical relevance of TP53 germline mutations in a large unselected breast cancer series are largely unknown. Here, we determined TP53 germline mutations in a large cohort of 10,053 unselected breast cancer patients through multigene panel-based next-generation and/or Sanger sequencing assays. We fo...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32424

    authors: Sheng S,Xu Y,Guo Y,Yao L,Hu L,Ouyang T,Li J,Wang T,Fan Z,Fan T,Lin B,Xie Y

    更新日期:2020-01-15 00:00:00

  • Biallelic deletion within 16p13.13 including SOCS-1 in Karpas1106P mediastinal B-cell lymphoma line is associated with delayed degradation of JAK2 protein.

    abstract::Activity of Janus kinase 2 (JAK2) in the JAK2/STAT5 signaling pathway is critically controlled by suppressor of cytokine signaling-1 (SOCS-1). We have previously shown that SOCS-1 is biallelically mutated in the primary mediastinal B-cell lymphoma (PMBL) cell line MedB-1, resulting in impaired JAK2 degradation and sus...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21485

    authors: Melzner I,Weniger MA,Bucur AJ,Brüderlein S,Dorsch K,Hasel C,Leithäuser F,Ritz O,Dyer MJ,Barth TF,Möller P

    更新日期:2006-04-15 00:00:00

  • Distinct molecular landscapes between endometrioid and nonendometrioid uterine carcinomas.

    abstract::Endometrial carcinoma (EC) is traditionally characterized as endometrioid and nonendometrioid based on histopathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between Mar...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.30537

    authors: Jones NL,Xiu J,Chatterjee-Paer S,Buckley de Meritens A,Burke WM,Tergas AI,Wright JD,Hou JY

    更新日期:2017-03-15 00:00:00

  • Screening of human brain tumors for SV40-related T antigen.

    abstract::A series of 39 human brain tumors has been screened for the presence or absence of SV40-related T antigen by the direct and indirect immunoperoxidase methods. Two tumors of ependymal origin (malignant ependymoma, choroid plexus papilloma) revealed markedly positive nuclear staining for T antigen both in vivo and in vi...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910210104

    authors: Tabuchi K,Kirsch WM,Low M,Gaskin D,Van Buskirk J,Maa S

    更新日期:1978-01-15 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

  • Modification of the effect of C. parvum on macrophage activity and tumour growth by X-irradiation.

    abstract::The radiosensitivity of three forms of response to injection of C. parvum in mice has been investigated. The increase in phagocytin index evoked by IP or IV injection of 0.7 mg C. parvum (but not that evoked by 1.4 mg) was reduced but not abolished in mice given 350-500 rad whole-body irradiation 4 days before C. parv...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910170515

    authors: Woodruff MF,Ghaffar A,Whitehead VL

    更新日期:1976-05-15 00:00:00

  • Genome-wide profiling of normal gastric mucosa identifies Helicobacter pylori- and cancer-associated DNA methylome changes.

    abstract::The large geographic variations in the incidence of gastric cancer (GC) are likely due to differential environmental exposures, in particular to Helicobacter pylori (H. pylori) infection. We aimed to investigate the impact of H. pylori on the epigenome in normal gastric mucosa and methylation changes associated with c...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31381

    authors: Woo HD,Fernandez-Jimenez N,Ghantous A,Degli Esposti D,Cuenin C,Cahais V,Choi IJ,Kim YI,Kim J,Herceg Z

    更新日期:2018-08-01 00:00:00

  • Mutation and expression of the p53 gene in malignant melanoma cell lines.

    abstract::Three monoclonal antibodies (MAbs) against p53 protein (PAb 24o, DO-I and PAb1801) were used to define the immunophenotype of 13 melanoma cell lines. Immunoreactions could be detected in 12 out of 13 cell lines by using the indirect immunofluorescence technique. In 7 of these the majority of cells displayed cytoplasmi...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910540427

    authors: Weiss J,Schwechheimer K,Cavenee WK,Herlyn M,Arden KC

    更新日期:1993-06-19 00:00:00

  • All-trans, 13-cis and 9-cis retinoic acids induce a fully reversible growth inhibition in HNSCC cell lines: implications for in vivo retinoic acid use.

    abstract::Retinoids are a group of vitamin A analogues that have shown promise as chemopreventive and therapeutic agents in many types of malignancy and have been entered in clinical trials with some successful results. To better understand the mechanism that mediates retinoid action and the anti-proliferative effects, we treat...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19970117)70:2<194::aid-ijc

    authors: Giannini F,Maestro R,Vukosavljevic T,Pomponi F,Boiocchi M

    更新日期:1997-01-17 00:00:00

  • Acquisition of immunogenicity by AKR leukemic cells following DNA-mediated gene transfer is associated with the reduction of constitutive reactive superoxide radicals.

    abstract::We have employed the DNA-mediated gene transfer method to introduce the allogenic major-histocompatibility-complex(MHC)-class-I gene H-2Kb into the K36.16 tumor cells, H-2k, in order to generate tumor-specific immunity. The acquisition of immunogenicity by the H-2Kb-transformed clones following gene transfer is associ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910570215

    authors: Chia KY,Lim SP,Oei AA,Sabapathy TK,Hui KM

    更新日期:1994-04-15 00:00:00

  • Direct comparison of liquid-based and conventional cytology in a South African screening trial.

    abstract::Our study directly compares the performance of liquid-based (LBC) and conventional cytology for detecting high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) in high-risk, previously unscreened women. As part of a larger randomized clinical trial assessing the efficacy and safety of a "screen and treat" ...

    journal_title:International journal of cancer

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/ijc.21434

    authors: Taylor S,Kuhn L,Dupree W,Denny L,De Souza M,Wright TC Jr

    更新日期:2006-02-15 00:00:00

  • Karyotypic characterization of bronchial large cell carcinomas.

    abstract::Cytogenetic analysis of short-term cultures from 26 primary bronchial large cell carcinomas and 1 metastasis from a primary large cell carcinoma revealed clonal chromosome abnormalities in 20 tumors and a normal karyotype in 6. No outgrowth was obtained in 1 case. Simple aberrations were present in 3 tumors; in 1, the...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910570404

    authors: Johansson M,Dietrich C,Mandahl N,Hambraeus G,Johansson L,Clausen PP,Mitelman F,Heim S

    更新日期:1994-05-15 00:00:00

  • Type of alcoholic beverage and cancer of the oral cavity, pharynx and oesophagus in an Italian area with high wine consumption.

    abstract::The role of different types of alcoholic beverage on cancer of the upper digestive tract was investigated in a case-control study conducted in the northern part of Italy on 305 male cases of cancer of the oral cavity and pharynx, 288 of oesophageal cancer and 1621 controls admitted to hospital for acute, non-neoplasti...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910460612

    authors: Barra S,Franceschi S,Negri E,Talamini R,La Vecchia C

    更新日期:1990-12-15 00:00:00

  • MicroRNA alterations in head and neck squamous cell carcinoma.

    abstract::MicroRNAs (mirs) are small noncoding RNA molecules (~22 nucleotides) that regulate posttranscriptional gene expression. Currently, there has not been a comprehensive study of their role in primary head and neck squamous cell carcinoma (HNSCC). To determine the role of mirs in HNSCC, we screened for altered microRNA ex...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23831

    authors: Chang SS,Jiang WW,Smith I,Poeta LM,Begum S,Glazer C,Shan S,Westra W,Sidransky D,Califano JA

    更新日期:2008-12-15 00:00:00

  • EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes.

    abstract::The hepatitis B virus (HBV) is a major causative agent of chronic liver disease and subsequent liver cirrhosis worldwide. The reduced sensitivity of virus-infected liver cells to apoptosis may play a role in the failure to remove virus-infected cells and eventually promote viral chronicity. The purpose of our study wa...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23921

    authors: Barreiros AP,Sprinzl M,Rosset S,Höhler T,Otto G,Theobald M,Galle PR,Strand D,Strand S

    更新日期:2009-01-01 00:00:00

  • An estimate of the proportion of colo-rectal and stomach cancers which might be prevented by certain changes in dietary habits.

    abstract::The colo-rectum and stomach are the 2 sites for which the role of diet in the etiology of cancer is most heavily implicated. Quantitative estimates as to the proportion of cancer deaths attributable to diet vary considerably. This may be partially due to the application of the concept of population attributable risk w...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910400509

    authors: Wahrendorf J

    更新日期:1987-11-15 00:00:00

  • Immunogenicity of recombinant GA733-2E antigen (CO17-1A, EGP, KS1-4, KSA, Ep-CAM) in gastro-intestinal carcinoma patients.

    abstract::Targeting the GA733 antigen (also known as CO17-1A, EGP, KS1-4, KSA, Ep-CAM) by monoclonal antibody CO17-1A or anti-idiotypic antibodies mimicking the CO17-1A or GA733 epitope has induced prolonged survival and specific immune responses to the antigen, respectively, in colorectal cancer (CRC) patients. In pre-clinical...

    journal_title:International journal of cancer

    pub_type: 临床试验,杂志文章

    doi:

    authors: Staib L,Birebent B,Somasundaram R,Purev E,Braumüller H,Leeser C,Küttner N,Li W,Zhu D,Diao J,Wunner W,Speicher D,Beger HG,Song H,Herlyn D

    更新日期:2001-04-01 00:00:00

  • An immunohistological method for estimating cell growth fractions in rapid histopathological diagnosis during surgery.

    abstract::In the past, it has been impossible to carry out immunohistological staining as part of a rapid histopathological diagnosis during surgery because the available methods were too time-consuming. The present report introduces a rapid indirect immunoperoxidase method that requires only 10-12 min. Thus, the immunological ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910350205

    authors: Gerdes J

    更新日期:1985-02-15 00:00:00

  • Human papillomavirus--the most significant risk determinant of cervical intraepithelial neoplasia.

    abstract::Sexual behavior has been consistently identified as a major risk factor for cervical cancer. Population-based studies have demonstrated that risk related to sexual activity is mediated by human papillomavirus (HPV) infection. We conducted a case-control study of 199 cases with low-grade squamous intraepithelial lesion...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0215(19960301)65:5<601::AID-IJC

    authors: Kjaer SK,van den Brule AJ,Bock JE,Poll PA,Engholm G,Sherman ME,Walboomers JM,Meijer CJ

    更新日期:1996-03-01 00:00:00

  • Sulfonated aluminium phthalocyanines as sensitizers for photochemotherapy. Effects of small light doses on localization, dye fluorescence and photosensitivity in V79 cells.

    abstract::V79 cells incubated with di- or tetrasulfonated aluminium phthalocyanines (AlPcS2 or AlPcS4) showed a granular fluorescence pattern. Co-staining with the lysosomotropic dye acridine orange (AO) indicated that the granules that were stained by these photoactive phthalocyanines were identical to lysosomes. Small light e...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910580620

    authors: Moan J,Berg K,Anholt H,Madslien K

    更新日期:1994-09-15 00:00:00

  • Site distribution of different types of skin cancer: new aetiological clues.

    abstract::Since the investigation, at an individual level, of lifetime sun exposure remains difficult the site distribution of different types of skin cancer can be an important source of aetiological clues. The present report deals with 1,149 cases of cutaneous malignant melanoma (CMM), 7,685 of basal-cell carcinoma (BCC) and ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0215(19960703)67:1<24::AID-IJC6

    authors: Franceschi S,Levi F,Randimbison L,La Vecchia C

    更新日期:1996-07-03 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

  • Selective inhibition of PED protein expression sensitizes B-cell chronic lymphocytic leukaemia cells to TRAIL-induced apoptosis.

    abstract::B-cell chronic lymphocytic leukaemia (B-CLL) cells fail to undergo apoptosis. The mechanism underlying this resistance to cell death is still largely unknown. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively kills tumour cells but not normal cells, and thus represents an attractive tool for...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22495

    authors: Garofalo M,Romano G,Quintavalle C,Romano MF,Chiurazzi F,Zanca C,Condorelli G

    更新日期:2007-03-15 00:00:00

  • Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination.

    abstract::NY-ESO-1 antigen is a prototype of a class of cancer/testis antigens. We carried out a clinical trial using NY-ESO-1 whole protein as a cancer vaccine for 13 advanced cancer patients. We have recently reported that vaccine elicited humoral and cellular immune responses in 9 cancer patients including 4 esophageal cance...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23810

    authors: Wada H,Sato E,Uenaka A,Isobe M,Kawabata R,Nakamura Y,Iwae S,Yonezawa K,Yamasaki M,Miyata H,Doki Y,Shiku H,Jungbluth AA,Ritter G,Murphy R,Hoffman EW,Old LJ,Monden M,Nakayama E

    更新日期:2008-11-15 00:00:00

  • Synthetic siRNA targeting the breakpoint of EWS/Fli-1 inhibits growth of Ewing sarcoma xenografts in a mouse model.

    abstract::The EWS/Fli-1 fusion gene, a product of the translocation t(11;22, q24;q12), is detected in 85% of Ewing sarcomas and primitive neuroectodermal tumors. It is thought to be a transcriptional activator that plays a significant role in tumorigenesis. In this study, we developed a novel EWS/Fli-1 blockade system using RNA...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25564

    authors: Takigami I,Ohno T,Kitade Y,Hara A,Nagano A,Kawai G,Saitou M,Matsuhashi A,Yamada K,Shimizu K

    更新日期:2011-01-01 00:00:00

  • DNA adducts in urothelial cells: relationship with biomarkers of exposure to arylamines and polycyclic aromatic hydrocarbons from tobacco smoke.

    abstract::Markers of exposure to polycyclic aromatic hydrocarbons (urinary 1-hydroxypyrene-glucuronide) and aromatic amines (4-aminobiphenyl-hemoglobin adducts), as well as urinary mutagenicity, were measured in 47 healthy smokers and 50 nonsmokers. DNA adducts were determined by P32-postlabeling in the exfoliated bladder cells...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(SICI)1097-0215(19960126)65:3<314::AID-IJC

    authors: Vineis P,Talaska G,Malaveille C,Bartsch H,Martone T,Sithisarankul P,Strickland P

    更新日期:1996-01-26 00:00:00