Castration induces autoantibody and T cell responses that correlate with inferior outcomes in an androgen-dependent murine tumor model.

Abstract:

:We recently reported that hormone therapy induces antigen-specific autoantibody responses in prostate cancer patients. However, the contribution of autoantibody responses to clinical outcomes is unknown. We used an animal model to test the hypothesis that hormone therapy-induced immune responses may be associated with delayed tumor recurrence. Male DD/S mice bearing established tumors from the androgen-dependent Shionogi carcinoma line were castrated to induce tumor regression. Tumor-specific autoantibody responses were measured by immunoblot, and the underlying antigen was identified by serological screening of a cDNA expression library. T cell responses were assessed by immunohistochemistry and IFN-gamma ELISPOT. Following castration, 97% of mice underwent complete tumor regression. Of these, 72% experienced tumor recurrence 18-79 days postcastration, whereas the remaining 28% remained tumor-free for the duration of the experiment. In 55% of mice, castration induced autoantibody responses to an antigen identified as poly(A) binding protein nuclear 1 (PABPN1). Castration also induced PABPN1-specific T cell responses, which were highly correlated to autoantibody responses, and this was accompanied by dense infiltration of tumors by CD3+ T cells 1-2 weeks after castration. Unexpectedly, mice that developed autoantibody and T cell responses to PABPN1 showed a higher rate and shorter latency of tumor recurrence. In mice with recurrent tumors, T cell responses to PABPN1 were still detectable; however, T cell infiltrates were restricted to the peripheral stroma of tumors. In conclusion, castration-induced immune responses are associated with inferior outcomes in the Shionogi carcinoma model, raising concerns about the influence of treatment-induced immune responses on clinical outcomes in humans.

journal_name

Int J Cancer

authors

Hahn S,Nesslinger NJ,Drapala RJ,Bowden M,Rennie PS,Pai HH,Ludgate C,Nelson BH

doi

10.1002/ijc.24673

subject

Has Abstract

pub_date

2009-12-15 00:00:00

pages

2871-8

issue

12

eissn

0020-7136

issn

1097-0215

journal_volume

125

pub_type

杂志文章
  • Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers.

    abstract::An important method for silencing tumor suppressor genes in cancers is by aberrant methylation (referred to as methylation) of CpG islands in gene promoter regions. In lung cancer, methylation of the genes retinoic acid receptor beta-2 (RARbeta-2), CDH13 (H-cadherin), p16(INK4a) (p16), RASSF1A (RAS association domain ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.11458

    authors: Zöchbauer-Müller S,Lam S,Toyooka S,Virmani AK,Toyooka KO,Seidl S,Minna JD,Gazdar AF

    更新日期:2003-11-20 00:00:00

  • Comparison of 131I-labelled anti-episialin 139H2 with cisplatin, cyclophosphamide or external-beam radiation for anti-tumor efficacy in human ovarian cancer xenografts.

    abstract::Three human ovarian cancer xenografts of different origin and grown s.c. in nude mice as well-established tumors were studied for their sensitivity to cisplatin (CDDP), cyclophosphamide (CTX), 131I-labelled anti-episialin monoclonal antibody (MAb) 139H2, or external-beam radiotherapy. The maximum tolerated dose of CDD...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910510120

    authors: Molthoff CF,Pinedo HM,Schlüper HM,Rutgers DH,Boven E

    更新日期:1992-04-22 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

  • Androgen receptor-interacting protein HSPBAP1 facilitates growth of prostate cancer cells in androgen-deficient conditions.

    abstract::Hormonal therapies targeting androgen receptor (AR) are effective in prostate cancer (PCa), but often the cancers progress to fatal castrate-resistant disease. Improved understanding of the cellular events during androgen deprivation would help to identify survival and stress pathways whose inhibition could synergize ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29303

    authors: Saeed K,Östling P,Björkman M,Mirtti T,Alanen K,Vesterinen T,Sankila A,Lundin J,Lundin M,Rannikko A,Nordling S,Mpindi JP,Kohonen P,Iljin K,Kallioniemi O,Rantala JK

    更新日期:2015-06-01 00:00:00

  • Enhancement by TPA of phenotypes associated with transformation in carcinogen-treated human cells: evidence for a selective mechanism.

    abstract::The tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) was found to increase the incidence of phenotypic alterations induced by the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in human endometrial stromal cells. Following carcinogen treatment, changes in saturation density, gamma-glutam...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910320405

    authors: Siegfried JM,Kaufman DG

    更新日期:1983-10-15 00:00:00

  • Changes in glycolipids in human renal-cell carcinoma and their clinical significance.

    abstract::The expression patterns of glycolipids of human renal-cell carcinoma were studied in primary tumors from 23 cases and 5 metastatic lesions from 4 cases using HPTLC (high-performance thin-layer chromatography). The expression pattern of glycolipids in primary tumors was characteristic of the histological cell type. In ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910490303

    authors: Saito S,Orikasa S,Ohyama C,Satoh M,Fukushi Y

    更新日期:1991-09-30 00:00:00

  • Radiation-induced expression of functional Fas ligand in EBV-positive human nasopharyngeal carcinoma cells.

    abstract::Ionizing radiation remains a major therapeutic tool against human cancers, especially epithelial tumors, which account for the majority of human malignancies. Although Fas and Fas-L are essential determinants of apoptosis, few data support their role in the cytotoxic effect of ionizing radiation. Epstein-Barr-virus (E...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(20000415)86:2<229::aid-ijc

    authors: Abdulkarim B,Sabri S,Deutsch E,Vaganay S,Marangoni E,Vainchenker W,Bongrand P,Busson P,Bourhis J

    更新日期:2000-04-15 00:00:00

  • Human natural killer cells promote cross-presentation of tumor cell-derived antigens by dendritic cells.

    abstract::Dendritic cells (DCs) cross-present antigen (Ag) to initiate T-cell immunity against most infections and tumors. Natural killer (NK) cells are innate cytolytic lymphocytes that have emerged as key modulators of multiple DC functions. Here, we show that human NK cells promote cross-presentation of tumor cell-derived Ag...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.29087

    authors: Deauvieau F,Ollion V,Doffin AC,Achard C,Fonteneau JF,Verronese E,Durand I,Ghittoni R,Marvel J,Dezutter-Dambuyant C,Walzer T,Vie H,Perrot I,Goutagny N,Caux C,Valladeau-Guilemond J

    更新日期:2015-03-01 00:00:00

  • Paracrine sonic hedgehog signaling contributes significantly to acquired steroidogenesis in the prostate tumor microenvironment.

    abstract::Despite the substantial benefit of androgen deprivation therapy (ADT) for metastatic prostate cancer, patients often progress to castration-resistant disease (CRPC) that is more difficult to treat. CRPC is associated with renewed androgen receptor activity in tumor cells and restoration of tumor androgen levels throug...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.30450

    authors: Lubik AA,Nouri M,Truong S,Ghaffari M,Adomat HH,Corey E,Cox ME,Li N,Guns ES,Yenki P,Pham S,Buttyan R

    更新日期:2017-01-15 00:00:00

  • HER2/neu over-expression induces endothelial cell retraction.

    abstract::Over-expression of the HER2/neu (HER2) proto-oncogene in breast carcinoma imparts an enhanced metastatic potential. Metastasis requires escape of the tumor cell from the vasculature into subjacent tissue, a transmigration event across an endothelial cell (EC) monolayer. EC retraction has been reported to precede trans...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/1097-0215(200002)9999:9999<::aid-ijc1061>3

    authors: Carter WB,Hoying JB,Boswell C,Williams SK

    更新日期:2001-02-01 00:00:00

  • No evidence for simian virus 40 DNA sequences in malignant non-Hodgkin lymphomas.

    abstract::DNA sequences coding for simian virus 40 (SV40) large T antigen have been detected at different frequencies in human non-Hodgkin's lymphomas (NHL) by PCR techniques as well as immunohistochemistry. A highly sensitive quantitative real-time PCR specific for a sequence of SV40 large T antigen was established to test whe...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21346

    authors: Schüler F,Dölken SC,Hirt C,Dölken MT,Mentel R,Gürtler LG,Dölken G

    更新日期:2006-01-15 00:00:00

  • Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors.

    abstract::Deletions on chromosomes 1p and 19q are associated with favorable prognosis in patients with oligodendroglial tumors. The aim of our study was to identify additional genomic aberrations linked to patient survival. We performed a genome-wide screen for genomic imbalances by comparative genomic hybridization on tumors f...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22574

    authors: Trost D,Ehrler M,Fimmers R,Felsberg J,Sabel MC,Kirsch L,Schramm J,Wiestler OD,Reifenberger G,Weber RG

    更新日期:2007-06-01 00:00:00

  • Cell death induced by N-(4-hydroxyphenyl)retinamide in human epidermal keratinocytes is modulated by TGF-beta and diminishes during the progression of squamous cell carcinoma.

    abstract::It has been demonstrated that the chemopreventive agent N-(4-hydroxyphenyl)retinamide (4-HPR) induces apoptotic cell death, but recent data has suggested that late stage/recurrent tumours lose their response to 4-HPR-induced cell death by mechanisms that are unknown. Our study investigated the ability of 4-HPR to indu...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22263

    authors: Davies M,Paterson IC,Ganapathy A,Prime SS

    更新日期:2006-12-15 00:00:00

  • Intravascular HBO(2) saturations, perfusion and hypoxia in spontaneous and transplanted tumor models.

    abstract::Clinical trials utilizing strategies to manipulate tumor oxygenation, blood flow and angiogenesis are under way, although limited quantitative information exists regarding basic tumor pathophysiology. The current study utilized murine KHT fibrosarcomas, spontaneous mammary carcinomas and first-generation spontaneous t...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.1401

    authors: Fenton BM,Lord EM,Paoni SF

    更新日期:2001-09-01 00:00:00

  • Acid ceramidase-mediated production of sphingosine 1-phosphate promotes prostate cancer invasion through upregulation of cathepsin B.

    abstract::Invasiveness is one of the key features of aggressive prostate cancer; however, our understanding of the precise mechanisms effecting invasion remains limited. The ceramide hydrolyzing enzyme acid ceramidase (AC), overexpressed in most prostate tumors, causes an aggressive and invasive phenotype through downstream eff...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.27480

    authors: Beckham TH,Lu P,Cheng JC,Zhao D,Turner LS,Zhang X,Hoffman S,Armeson KE,Liu A,Marrison T,Hannun YA,Liu X

    更新日期:2012-11-01 00:00:00

  • Effect of epidermal growth factor on clonogenic growth of primary human tumor cells.

    abstract::The effect of EGF on the soft agar colony-forming ability of fresh human tumor cells was assessed in 40 specimens obtained from various types of carcinoma including those of the breast, endometrium ovary, and other sites. Cells from four established human tumor cell lines (three breast and one endometrial) were also i...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910300611

    authors: Pathak MA,Matrisian LM,Magun BE,Salmon SE

    更新日期:1982-12-15 00:00:00

  • Immunogenic properties of retroviral protein P15E from drug-treated murine mastocytoma P815.

    abstract::A triazene-xenogenized tumor sub-line was derived from the mouse mastocytoma cell line P815 following several transplant generations in vivo on DTIC. The highly immunogenic P815/DTIC variant line expressed new CTL-defined antigens. Novel antigens were also detected by antibodies in immunoprecipitation and by Western b...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910550227

    authors: Grohmann U,Fioretti MC,Binaglia L,Belladonna ML,Bianchi R,Puccetti P

    更新日期:1993-09-09 00:00:00

  • Suppressing effects of dietary supplementation of soybean trypsin inhibitor on spontaneous, experimental and peritoneal disseminated metastasis in mouse model.

    abstract::The modifying effects of a Kunitz trypsin inhibitor (KTI) and a Bowman-Birk trypsin inhibitor (BBI), purified from soybean trypsin inhibitor, as dietary supplements on experimental and spontaneous pulmonary metastasis of murine Lewis lung carcinoma 3LL cells as well as peritoneal disseminated metastasis model in human...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20430

    authors: Kobayashi H,Fukuda Y,Yoshida R,Kanada Y,Nishiyama S,Suzuki M,Kanayama N,Terao T

    更新日期:2004-11-10 00:00:00

  • Lipid peroxidation and DNA adduct formation in lymphocytes of premenopausal women: Role of estrogen metabolites and fatty acid intake.

    abstract::A diet high in linoleic acid (an ω-6 PUFA) increased the formation of miscoding etheno (ε)--DNA adducts in WBC-DNA of women, but not in men (Nair et al., Cancer Epidemiol Biomark Prev 1997;6:597-601). This gender specificity could result from an interaction between ω-6 PUFA intake and estrogen catabolism, via redox-cy...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.27479

    authors: Sun X,Nair J,Linseisen J,Owen RW,Bartsch H

    更新日期:2012-11-01 00:00:00

  • Preserved foods and nasopharyngeal carcinoma: a case-control study among Singapore Chinese.

    abstract::The association between the consumption of preserved foods in infancy, childhood and adulthood and the risk of nasopharyngeal carcinoma was investigated in a case-control study among Singapore Chinese: 200 cases (73% male) were compared with 406 hospital controls (71% male). Significantly increased risks were observed...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910590502

    authors: Lee HP,Gourley L,Duffy SW,Esteve J,Lee J,Day NE

    更新日期:1994-12-01 00:00:00

  • SET complex in serous epithelial ovarian cancer.

    abstract::With low cure rates but increasing diverse treatment options that provide variable remission times, ovarian cancer is increasingly being recognized as a chronic disease. This reality indicates the need for a better understanding of factors influencing disease progression. In a previous global analysis of gene expressi...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.22054

    authors: Ouellet V,Le Page C,Guyot MC,Lussier C,Tonin PN,Provencher DM,Mes-Masson AM

    更新日期:2006-11-01 00:00:00

  • Simultaneous presence of EBNA-positive and colony-forming cells in peripheral blood of patients with infectious mononucleosis.

    abstract::EBNA-positive lymphoblast cells were detected in 0.1 to 0.9% of the T-cell-depleted lymphocytes obtained from peripheral blood samples of five patients with infectious mononucleosis (IM). The same blood specimens from four of the five patients contained cells that formed EBNA-positive colonies in soft agar containing ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910230603

    authors: Katsuki T,Hinuma Y,Saito T,Yamamoto J,Hirashima Y,Sudoh H,Deguchi M,Motokawa M

    更新日期:1979-06-15 00:00:00

  • Changes in lung-cancer mortality trends in Spain.

    abstract::Several changes in smoking patterns over the past decades in Spain can be expected to result in a shift in lung-cancer mortality rates. We examined time trends in lung-cancer mortality from 1973-1997 using a log-linear Poisson age-period-cohort model. The standardized lung-cancer mortality rate for men almost doubled,...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.1575

    authors: Franco J,Pérez-Hoyos S,Plaza P

    更新日期:2002-01-01 00:00:00

  • Deficiency in surface expression of E-selectin ligand promotes lung colonization in a mouse model of breast cancer.

    abstract::Expression of sialyl Lewis(x) (sLe(x)) and sLe(a) on tumor cells is thought to facilitate metastasis by promoting cell adhesion to selectins on vascular endothelial cells. Experiments supporting this concept usually bypass the early steps of the metastatic process by employing tumor cells that are injected directly in...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.21192

    authors: Monzavi-Karbassi B,Whitehead TL,Jousheghany F,Artaud C,Hennings L,Shaaf S,Slaughter A,Korourian S,Kelly T,Blaszczyk-Thurin M,Kieber-Emmons T

    更新日期:2005-11-10 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

  • Differential intracellular processing of the anthracycline drug ME2303 in doxorubicin-sensitive (A2780) and -resistant (A2780AD) human ovarian cancer cells as studied with confocal laser scanning microscopy and image analysis.

    abstract::Laser scanning confocal microscopy has been used to follow the uptake and efflux of the 2-fluoroglycoside of doxorubicin, ME2303, in live cultures of the human ovarian cancer cell line A2780 and its doxorubicin-resistant variant A2780AD. Our methods combine confocal laser scanning microscopy and image analysis to exam...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910590118

    authors: Huxham IM,Barlow AL,Lewis AD,Plumb J,Mairs RJ,Gaze MN,Workman P

    更新日期:1994-10-01 00:00:00

  • TMZ-induced PrPc/par-4 interaction promotes the survival of human glioma cells.

    abstract::Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ), has demonstrated promising activity against gliomas, the effects last only a few months and drug resistance develops thereafter in many cases. It has been acknowledged th...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25985

    authors: Zhuang D,Liu Y,Mao Y,Gao L,Zhang H,Luan S,Huang F,Li Q

    更新日期:2012-01-15 00:00:00

  • Weight change, obesity and risk of prostate cancer progression among men with clinically localized prostate cancer.

    abstract::Obesity is associated with an increased risk of fatal prostate cancer. We aimed to elucidate the importance and relevant timing of obesity and weight change for prostate cancer progression. We identified 5,158 men diagnosed with localized prostate cancer (clinical stage T1/T2) from 1986 to 2012 in the Health Professio...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.30803

    authors: Dickerman BA,Ahearn TU,Giovannucci E,Stampfer MJ,Nguyen PL,Mucci LA,Wilson KM

    更新日期:2017-09-01 00:00:00

  • Arsenic trioxide sensitizes CD95/Fas-induced apoptosis through ROS-mediated upregulation of CD95/Fas by NF-kappaB activation.

    abstract::CD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in sensitive cells. Therefore, modalities to regulate the CD95/Fas expression level in tumor cells are called for. In the present study, we show that sublethal doses of ar...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20433

    authors: Woo SH,Park IC,Park MJ,An S,Lee HC,Jin HO,Park SA,Cho H,Lee SJ,Gwak HS,Hong YJ,Hong SI,Rhee CH

    更新日期:2004-11-20 00:00:00

  • Dosimetric analysis of urinary morbidity following prostate brachytherapy (125I vs. 103Pd) combined with external beam radiation therapy.

    abstract::The purpose of this analysis was to correlate isotope selection with the urinary symptoms of patients who received a combination of external beam radiotherapy (EBRT) and a transperineal interstitial permanent prostate brachytherapy (TIPPB) boost with either a (103)palladium ((103)Pd) or a (125)iodine ((125)I) radioiso...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10350

    authors: Chen CT,Waterman FM,Valicenti RK,Gomella LG,Strup SE,Dicker AP

    更新日期:2001-01-01 00:00:00