Oxygenation and response to irradiation of organotypic multicellular spheroids of human glioma

Peter Sminia, Helmut Acker, Hans Petter Eikesdal, Patricia Kaaijk, Per øvind Enger, Ben Slotman, Rolf Bjerkvig

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: Investigation of the oxygenation status of organotypic multicellular spheroids (OMS) and their response to irradiation.

MATERIALS AND METHODS: Tumour specimens of glioblastoma multiforme patients (n = 16) were initiated as OMS. Following 20 Gy gamma-irradiation, the cell migratory capacity was evaluated. Spheroid oxygenation was determined by micro-electrode pO2 measurements and pimonidazole immunostaining. Spheroids prepared from established human glioma cell lines were used as a reference.

RESULTS: Irradiation inhibited spheroid outgrowth by 12 to 88% relative to the non-irradiated controls. A large interpatient variation was noticed. Oxygen measurements revealed a gradual decrease in pO2 level from the periphery to the core of the spheroids, but the pO2 values remained within an oxygenated range. However, in the cell line spheroids an intermediate layer of hypoxia surrounding the central core was observed.

CONCLUSION: Cell line spheroids with a hypoxic cell fraction and well-oxygenated OMS both show high resistance to irradiation, indicating that hypoxia may not be the biological factor determining the radioresistance of glioma spheroids in vitro.

Original languageEnglish
Pages (from-to)1461-6
Number of pages6
JournalAnticancer Research
Volume23
Issue number2B
Publication statusPublished - 25 Jun 2003

Cite this

Sminia, P., Acker, H., Eikesdal, H. P., Kaaijk, P., Enger, P. Ø., Slotman, B., & Bjerkvig, R. (2003). Oxygenation and response to irradiation of organotypic multicellular spheroids of human glioma. Anticancer Research, 23(2B), 1461-6.
Sminia, Peter ; Acker, Helmut ; Eikesdal, Hans Petter ; Kaaijk, Patricia ; Enger, Per øvind ; Slotman, Ben ; Bjerkvig, Rolf. / Oxygenation and response to irradiation of organotypic multicellular spheroids of human glioma. In: Anticancer Research. 2003 ; Vol. 23, No. 2B. pp. 1461-6.
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abstract = "PURPOSE: Investigation of the oxygenation status of organotypic multicellular spheroids (OMS) and their response to irradiation.MATERIALS AND METHODS: Tumour specimens of glioblastoma multiforme patients (n = 16) were initiated as OMS. Following 20 Gy gamma-irradiation, the cell migratory capacity was evaluated. Spheroid oxygenation was determined by micro-electrode pO2 measurements and pimonidazole immunostaining. Spheroids prepared from established human glioma cell lines were used as a reference.RESULTS: Irradiation inhibited spheroid outgrowth by 12 to 88{\%} relative to the non-irradiated controls. A large interpatient variation was noticed. Oxygen measurements revealed a gradual decrease in pO2 level from the periphery to the core of the spheroids, but the pO2 values remained within an oxygenated range. However, in the cell line spheroids an intermediate layer of hypoxia surrounding the central core was observed.CONCLUSION: Cell line spheroids with a hypoxic cell fraction and well-oxygenated OMS both show high resistance to irradiation, indicating that hypoxia may not be the biological factor determining the radioresistance of glioma spheroids in vitro.",
keywords = "Brain Neoplasms/pathology, Cell Division/radiation effects, Cell Hypoxia, Cell Movement/radiation effects, DNA Adducts/analysis, DNA, Neoplasm/analysis, Gamma Rays, Glioblastoma/pathology, Humans, Microscopy, Confocal, Nitroimidazoles/pharmacology, Oxygen/metabolism, Partial Pressure, Radiation Tolerance, Spheroids, Cellular/metabolism",
author = "Peter Sminia and Helmut Acker and Eikesdal, {Hans Petter} and Patricia Kaaijk and Enger, {Per {\o}vind} and Ben Slotman and Rolf Bjerkvig",
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Sminia, P, Acker, H, Eikesdal, HP, Kaaijk, P, Enger, PØ, Slotman, B & Bjerkvig, R 2003, 'Oxygenation and response to irradiation of organotypic multicellular spheroids of human glioma' Anticancer Research, vol. 23, no. 2B, pp. 1461-6.

Oxygenation and response to irradiation of organotypic multicellular spheroids of human glioma. / Sminia, Peter; Acker, Helmut; Eikesdal, Hans Petter; Kaaijk, Patricia; Enger, Per øvind; Slotman, Ben; Bjerkvig, Rolf.

In: Anticancer Research, Vol. 23, No. 2B, 25.06.2003, p. 1461-6.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Oxygenation and response to irradiation of organotypic multicellular spheroids of human glioma

AU - Sminia, Peter

AU - Acker, Helmut

AU - Eikesdal, Hans Petter

AU - Kaaijk, Patricia

AU - Enger, Per øvind

AU - Slotman, Ben

AU - Bjerkvig, Rolf

PY - 2003/6/25

Y1 - 2003/6/25

N2 - PURPOSE: Investigation of the oxygenation status of organotypic multicellular spheroids (OMS) and their response to irradiation.MATERIALS AND METHODS: Tumour specimens of glioblastoma multiforme patients (n = 16) were initiated as OMS. Following 20 Gy gamma-irradiation, the cell migratory capacity was evaluated. Spheroid oxygenation was determined by micro-electrode pO2 measurements and pimonidazole immunostaining. Spheroids prepared from established human glioma cell lines were used as a reference.RESULTS: Irradiation inhibited spheroid outgrowth by 12 to 88% relative to the non-irradiated controls. A large interpatient variation was noticed. Oxygen measurements revealed a gradual decrease in pO2 level from the periphery to the core of the spheroids, but the pO2 values remained within an oxygenated range. However, in the cell line spheroids an intermediate layer of hypoxia surrounding the central core was observed.CONCLUSION: Cell line spheroids with a hypoxic cell fraction and well-oxygenated OMS both show high resistance to irradiation, indicating that hypoxia may not be the biological factor determining the radioresistance of glioma spheroids in vitro.

AB - PURPOSE: Investigation of the oxygenation status of organotypic multicellular spheroids (OMS) and their response to irradiation.MATERIALS AND METHODS: Tumour specimens of glioblastoma multiforme patients (n = 16) were initiated as OMS. Following 20 Gy gamma-irradiation, the cell migratory capacity was evaluated. Spheroid oxygenation was determined by micro-electrode pO2 measurements and pimonidazole immunostaining. Spheroids prepared from established human glioma cell lines were used as a reference.RESULTS: Irradiation inhibited spheroid outgrowth by 12 to 88% relative to the non-irradiated controls. A large interpatient variation was noticed. Oxygen measurements revealed a gradual decrease in pO2 level from the periphery to the core of the spheroids, but the pO2 values remained within an oxygenated range. However, in the cell line spheroids an intermediate layer of hypoxia surrounding the central core was observed.CONCLUSION: Cell line spheroids with a hypoxic cell fraction and well-oxygenated OMS both show high resistance to irradiation, indicating that hypoxia may not be the biological factor determining the radioresistance of glioma spheroids in vitro.

KW - Brain Neoplasms/pathology

KW - Cell Division/radiation effects

KW - Cell Hypoxia

KW - Cell Movement/radiation effects

KW - DNA Adducts/analysis

KW - DNA, Neoplasm/analysis

KW - Gamma Rays

KW - Glioblastoma/pathology

KW - Humans

KW - Microscopy, Confocal

KW - Nitroimidazoles/pharmacology

KW - Oxygen/metabolism

KW - Partial Pressure

KW - Radiation Tolerance

KW - Spheroids, Cellular/metabolism

M3 - Article

VL - 23

SP - 1461

EP - 1466

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 2B

ER -