Hormonal effects on glioblastoma multiforme in the nude rat model

Restricted access

Object. The authors studied the effect of gender and hormonal status on survival in nude rats implanted with human glioblastoma multiforme (GBM) cell lines.

Methods. Nude rats received intracerebral implants of either wild-type U87MG cells or U87MG cells transfected with the gene for endothelin-1 (U87/ET-1). In the initial study, survival was compared in males and females for each of the two cell lines. The six second-phase study groups were composed of: 1) males; 2) females; 3) ovariectomized females; 4) sham ovariectomized females; 5) ovariectomized rats given 10 µg/day estradiol benzoate for 21 days; and 6) ovariectomized rats given 20 mg/kg/day progesterone for 21 days. All rats in the second phase were implanted with U87/ET-1 cells. Animals were killed when they exhibited initial signs of neurological deterioration. Female nude rats survived longer than male rats implanted with either U87 or U87/ET-1 cells. In the second phase, ovariectomized, male, and progesterone-treated rats died at approximately 19 days, whereas the female, sham-treated, and estrogen-treated animals died 23 to 25 days after tumor cell implantation.

Conclusions. The authors demonstrate that female nude rats implanted with human GBM cells have a survival advantage over male rats and that estrogen provides the advantage.

Article Information

Contributor Notes

Address reprint requests to: Robert J. Plunkett, M.D., Department of Neurosurgery, State University of New York at Buffalo, 100 High Street, E-2, Buffalo, New York 14203. email: rjp@pce.net.
Headings
References
  • 1.

    Avtsyn APYablonovskayan LY: Effects of disturbances in the hormone status on experimental brain tumors. Acta UN Int Canc 20:151915221964Avtsyn AP Yablonovskayan LY: Effects of disturbances in the hormone status on experimental brain tumors. Acta UN Int Canc 20:1519–1522 1964

    • Search Google Scholar
    • Export Citation
  • 2.

    Barth RF: Rat brain tumor models in experimental neuro-oncology: the 9L, C6, T9, F98, RG2 (D74), RT-2 and CNS-1 gliomas. J Neurooncol 36:911021998Barth RF: Rat brain tumor models in experimental neuro-oncology: the 9L C6 T9 F98 RG2 (D74) RT-2 and CNS-1 gliomas. J Neurooncol 36:91–102 1998

    • Search Google Scholar
    • Export Citation
  • 3.

    Bigner DDBigner SHBurger PCet al: Primary brain tumours in Fischer 344 rats chronically exposed to acrylonitrile in their drinking-water. Food Chem Toxicol 24:1291371986Bigner DD Bigner SH Burger PC et al: Primary brain tumours in Fischer 344 rats chronically exposed to acrylonitrile in their drinking-water. Food Chem Toxicol 24:129–137 1986

    • Search Google Scholar
    • Export Citation
  • 4.

    Carroll RSZhang JDashner Ket al: Steroid hormone receptors in astrocytic neoplasms. Neurosurgery 37:4965041995Carroll RS Zhang J Dashner K et al: Steroid hormone receptors in astrocytic neoplasms. Neurosurgery 37:496–504 1995

    • Search Google Scholar
    • Export Citation
  • 5.

    Chandler KLPrados MDMalec Met al: Long-term survival in patients with glioblastoma multiforme. Neurosurgery 32:7167201993Chandler KL Prados MD Malec M et al: Long-term survival in patients with glioblastoma multiforme. Neurosurgery 32:716–720 1993

    • Search Google Scholar
    • Export Citation
  • 6.

    Davis FGFreels SGrutsch Jet al: Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on surveillance, epidemiology, and end results (SEER) data, 1973–1991. J Neurosurg 88:1101998Davis FG Freels S Grutsch J et al: Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on surveillance epidemiology and end results (SEER) data 1973–1991. J Neurosurg 88:1–10 1998

    • Search Google Scholar
    • Export Citation
  • 7.

    Druckrey HIvanković SPreussmann R: Teratogenic and carcinogenic effects in the offspring after single injection of ethyl-nitrosourea to pregnant rats. Nature 210:137813791966Druckrey H Ivanković S Preussmann R: Teratogenic and carcinogenic effects in the offspring after single injection of ethyl-nitrosourea to pregnant rats. Nature 210:1378–1379 1966

    • Search Google Scholar
    • Export Citation
  • 8.

    Fitzgerald JESchardein JLKurtz SM: Spontaneous tumors of the nervous system in albino rats. J Natl Cancer Inst 52:2652731974Fitzgerald JE Schardein JL Kurtz SM: Spontaneous tumors of the nervous system in albino rats. J Natl Cancer Inst 52:265–273 1974

    • Search Google Scholar
    • Export Citation
  • 9.

    Fotsis TZhang YPepper MSet al: The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 368:2372391994Fotsis T Zhang Y Pepper MS et al: The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 368:237–239 1994

    • Search Google Scholar
    • Export Citation
  • 10.

    Fraser H: Brain tumours in mice, with particular reference to astrocytoma. Food Chem Toxicol 24:1051111986Fraser H: Brain tumours in mice with particular reference to astrocytoma. Food Chem Toxicol 24:105–111 1986

    • Search Google Scholar
    • Export Citation
  • 11.

    Garman RHSnellings WMMaronpot RR: Frequency, size and location of brain tumours in F-344 rats chronically exposed to ethylene oxide. Food Chem Toxicol 24:1451531986Garman RH Snellings WM Maronpot RR: Frequency size and location of brain tumours in F-344 rats chronically exposed to ethylene oxide. Food Chem Toxicol 24:145–153 1986

    • Search Google Scholar
    • Export Citation
  • 12.

    Gopinath C: Spontaneous brain tumours in Sprague-Dawley rats. Food Chem Toxicol 24:1131201986Gopinath C: Spontaneous brain tumours in Sprague-Dawley rats. Food Chem Toxicol 24:113–120 1986

    • Search Google Scholar
    • Export Citation
  • 13.

    Hirano HAsakura TYokoyama Set al: [The prognostic factors in astrocytic tumors: analysis by the Kaplan-Meier method and the Weibull log-linear model.] No Shinkei Geka 24:8098151996 (Jpn)Hirano H Asakura T Yokoyama S et al: [The prognostic factors in astrocytic tumors: analysis by the Kaplan-Meier method and the Weibull log-linear model.] No Shinkei Geka 24:809–815 1996 (Jpn)

    • Search Google Scholar
    • Export Citation
  • 14.

    Hopewell JW: The effects of castration on the induction of experimental gliomas in male rats. Br J Cancer 24:1871901970Hopewell JW: The Effects of castration on the induction of experimental gliomas in male rats. Br J Cancer 24:187–190 1970

    • Search Google Scholar
    • Export Citation
  • 15.

    Hopewell JW: The hormone dependence of experimentally induced gliomas in the rat. Neuropathol Appl Neurobiol 1:1411481975Hopewell JW: The hormone dependence of experimentally induced gliomas in the rat. Neuropathol Appl Neurobiol 1:141–148 1975

    • Search Google Scholar
    • Export Citation
  • 16.

    Ivankovic SDruckrey H: Transplacentare Erzeugung maligner Tumoren des Nervensystems. I. Athul-nitroso-harnstoff (ANH) an BD IX-Ratten. Z Krebsforsch 71:3203601968Ivankovic S Druckrey H: Transplacentare Erzeugung maligner Tumoren des Nervensystems. I. Athul-nitroso-harnstoff (ANH) an BD IX-Ratten. Z Krebsforsch 71:320–360 1968

    • Search Google Scholar
    • Export Citation
  • 17.

    Ivankovic SDruckrey HPreussmann R: Erzeugung neurogener Tumoren bei den Nachkommen nach einmaliger Injektion von Athylnitrosoharnstoff an schwangere Ratten. Naturwissenschaften 53:4101966Ivankovic S Druckrey H Preussmann R: Erzeugung neurogener Tumoren bei den Nachkommen nach einmaliger Injektion von Athylnitrosoharnstoff an schwangere Ratten. Naturwissenschaften 53:410 1966

    • Search Google Scholar
    • Export Citation
  • 18.

    Kallio MSankila RJääskeläinen Jet al: A population-based study on the incidence and survival rates of 3857 glioma patients diagnosed from 1953 to 1984. Cancer 68:139414001991Kallio M Sankila R Jääskeläinen J et al: A population-based study on the incidence and survival rates of 3857 glioma patients diagnosed from 1953 to 1984. Cancer 68:1394–1400 1991

    • Search Google Scholar
    • Export Citation
  • 19.

    Khalid HYasunaga AKishikawa Met al: Immunohistochemical expression of the estrogen receptor-related antigen (ER-D5) in human intracranial tumors. Cancer 75:257125781995Khalid H Yasunaga A Kishikawa M et al: Immunohistochemical expression of the estrogen receptor-related antigen (ER-D5) in human intracranial tumors. Cancer 75:2571–2578 1995

    • Search Google Scholar
    • Export Citation
  • 20.

    Kreth FWFaist MRossner Ret al: Supratentorial World Health Organization Grade 2 astrocytomas and oligoastrocytomas. A new pattern of prognostic factors. Cancer 79:3703791997Kreth FW Faist M Rossner R et al: Supratentorial World Health Organization Grade 2 astrocytomas and oligoastrocytomas. A new pattern of prognostic factors. Cancer 79:370–379 1997

    • Search Google Scholar
    • Export Citation
  • 21.

    Lee YBullard DEHumphrey PAet al: Treatment of intracranial human glioma xenografts with 131I-labeled anti-tenascin monoclonal antibody 81C6. Cancer Res 48:290429101988Lee Y Bullard DE Humphrey PA et al: Treatment of intracranial human glioma xenografts with 131I-labeled anti-tenascin monoclonal antibody 81C6. Cancer Res 48:2904–2910 1988

    • Search Google Scholar
    • Export Citation
  • 22.

    Mukhopadhyay TRoth JA: Induction of apoptosis in human lung cancer cells after wild-type p53 activation by methoxyestradiol. Oncogene 14:3793841997Mukhopadhyay T Roth JA: Induction of apoptosis in human lung cancer cells after wild-type p53 activation by methoxyestradiol. Oncogene 14:379–384 1997

    • Search Google Scholar
    • Export Citation
  • 23.

    Paxinos GWatson C: The Rat Brain in Stereotaxic Coordinatesed 2. San Diego: Academic Press1986Paxinos G Watson C: The Rat Brain in Stereotaxic Coordinates ed 2. San Diego: Academic Press 1986

    • Search Google Scholar
    • Export Citation
  • 24.

    Plunkett RJWeber RJOldfield EH: Stereotaxic implantation of dispersed cell suspensions into brain. A systematic appraisal of cell placement and survival. J Neurosurg 69:2282331988Plunkett RJ Weber RJ Oldfield EH: Stereotaxic implantation of dispersed cell suspensions into brain. A systematic appraisal of cell placement and survival. J Neurosurg 69:228–233 1988

    • Search Google Scholar
    • Export Citation
  • 25.

    Pollack IFRandall MSKristofik MPet al: Effect of tamoxifen on DNA synthesis and proliferation of human malignant glioma lines in vitro. Cancer Res 50:713471381990Pollack IF Randall MS Kristofik MP et al: Effect of tamoxifen on DNA synthesis and proliferation of human malignant glioma lines in vitro. Cancer Res 50:7134–7138 1990

    • Search Google Scholar
    • Export Citation
  • 26.

    Preston-Martin SMack WJ: Neoplasms of the nervous system in Schottenfeld DFraumeni JF Jr (eds): Cancer Epidemiology and Preventioned 2. New York: Oxford University Press1996 pp 12311281Preston-Martin S Mack WJ: Neoplasms of the nervous system in Schottenfeld D Fraumeni JF Jr (eds): Cancer Epidemiology and Prevention ed 2. New York: Oxford University Press 1996 pp 1231–1281

    • Search Google Scholar
    • Export Citation
  • 27.

    Roof RLDuvdevani RStein DG: Progesterone treatment attenuates brain edema following contusion injury in male and female rats. Restor Neurol Neurosci 4:4254271992Roof RL Duvdevani R Stein DG: Progesterone treatment attenuates brain edema following contusion injury in male and female rats. Restor Neurol Neurosci 4:425–427 1992

    • Search Google Scholar
    • Export Citation
  • 28.

    Roth JGElvidge AR: Glioblastoma multiforme: a clinical survey. J Neurosurg 17:7367501960Roth JG Elvidge AR: Glioblastoma multiforme: a clinical survey. J Neurosurg 17:736–750 1960

    • Search Google Scholar
    • Export Citation
  • 29.

    Salcman M: Glioblastoma and malignant astrocytoma in Kaye AHLaws ER Jr (eds): Brain Tumors: An Encyclopedic Approach. New York: Churchill Livingstone1995 pp 449478Salcman M: Glioblastoma and malignant astrocytoma in Kaye AH Laws ER Jr (eds): Brain Tumors: An Encyclopedic Approach. New York: Churchill Livingstone 1995 pp 449–478

    • Search Google Scholar
    • Export Citation
  • 30.

    Shibutani MMaekawa AOkeda Ret al: An experimental model for anaplastic astrocytomas and glioblastoma using adult F344 rats and N-methyl-N-nitrosourea. Acta Pathol Jpn 43:4644741993Shibutani M Maekawa A Okeda R et al: An experimental model for anaplastic astrocytomas and glioblastoma using adult F344 rats and N-methyl-N-nitrosourea. Acta Pathol Jpn 43:464–474 1993

    • Search Google Scholar
    • Export Citation
  • 31.

    Siesjo PVisse ESjögren HO: Cure of established, intracerebral rat gliomas induced by therapeutic immunizations with tumor cells and purified APC or adjuvant IFN-gamma treatment. J Immunother 19:3343451996Siesjo P Visse E Sjögren HO: Cure of established intracerebral rat gliomas induced by therapeutic immunizations with tumor cells and purified APC or adjuvant IFN-gamma treatment. J Immunother 19:334–345 1996

    • Search Google Scholar
    • Export Citation
  • 32.

    Velema JPPercy CL: Age curves of central nervous system tumor incidence in adults: variation of shape by histologic type. J Natl Cancer Inst 79:6236291987Velema JP Percy CL: Age curves of central nervous system tumor incidence in adults: variation of shape by histologic type. J Natl Cancer Inst 79:623–629 1987

    • Search Google Scholar
    • Export Citation
  • 33.

    Verzat CCourriere PHollande E: Heterotransplantation of a human oligoastrocytoma into nude mice: difference in tumour growth between males and females. Neuropathol Appl Neurobiol 18:37511992Verzat C Courriere P Hollande E: Heterotransplantation of a human oligoastrocytoma into nude mice: difference in tumour growth between males and females. Neuropathol Appl Neurobiol 18:37–51 1992

    • Search Google Scholar
    • Export Citation
  • 34.

    Verzat CDelisle MBCourriere Pet al: Influence of host sex on the growth of a human glioblastoma line in athymic mice. Neuropathol Appl Neurobiol 16:1411511990Verzat C Delisle MB Courriere P et al: Influence of host sex on the growth of a human glioblastoma line in athymic mice. Neuropathol Appl Neurobiol 16:141–151 1990

    • Search Google Scholar
    • Export Citation
  • 35.

    Ward JMRice JM: Naturally occurring and chemically induced brain tumors of rats and mice in carcinogenesis bioassays. Ann NY Acad Sci 381:3043191982Ward JM Rice JM: Naturally occurring and chemically induced brain tumors of rats and mice in carcinogenesis bioassays. Ann NY Acad Sci 381:304–319 1982

    • Search Google Scholar
    • Export Citation
  • 36.

    Zhu BTConney AH: Is 2-methoxyestradiol an endogenous estrogen metabolite that inhibits mammary carcinogenesis? Cancer Res 58:226922771998Zhu BT Conney AH: Is 2-methoxyestradiol an endogenous estrogen metabolite that inhibits mammary carcinogenesis? Cancer Res 58:2269–2277 1998

    • Search Google Scholar
    • Export Citation
  • 37.

    Zülch KJ: Brain Tumors: Their Biology and Pathology. Berlin: Springer-Verlag1986 pp 8795Zülch KJ: Brain Tumors: Their Biology and Pathology. Berlin: Springer-Verlag 1986 pp 87–95

    • Search Google Scholar
    • Export Citation
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 262 156 16
Full Text Views 149 12 0
PDF Downloads 124 7 0
EPUB Downloads 0 0 0
PubMed
Google Scholar