Radiation-Induced cancer cell repopulation: A possible mechanism implied by experiments using transplantable mouse-derived sarcoma cell line

Takeshi Nishioka, Motoaki Yasuda, Tsuguhide Takeshima, Hisashi Haga, Yusuke Miyai, Ken Ichiro Shibata, Rie Yamazaki, Hiroki Shirato, Masahiro Teduka, Hiroyuki Date

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. Materials and Methods: A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. Results: cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p<0.01, Student's t-test). Conclusions: This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalCell Structure and Function
Volume36
Issue number1
DOIs
StatePublished - 2011

Fingerprint

Radiation-Induced Neoplasms
Sarcoma
Clone Cells
Cell Line
Cyclin-Dependent Kinase Inhibitor p57
Complementary DNA
Transplantation
Cyclin-Dependent Kinase Inhibitor p16
Matrix Metalloproteinase 13
Matrix Metalloproteinase 3
Fibrosarcoma
Cytotoxins
Gene Expression Profiling
Organism Cloning
Cell Count
Students
Gene Expression
Light
Mutation
Genes

Keywords

  • Irradiation
  • Matrix metalloproteinase
  • P16
  • Radiotherapy
  • Repopulation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Radiation-Induced cancer cell repopulation : A possible mechanism implied by experiments using transplantable mouse-derived sarcoma cell line. / Nishioka, Takeshi; Yasuda, Motoaki; Takeshima, Tsuguhide; Haga, Hisashi; Miyai, Yusuke; Shibata, Ken Ichiro; Yamazaki, Rie; Shirato, Hiroki; Teduka, Masahiro; Date, Hiroyuki.

In: Cell Structure and Function, Vol. 36, No. 1, 2011, p. 13-20.

Research output: Contribution to journalArticle

Nishioka, T, Yasuda, M, Takeshima, T, Haga, H, Miyai, Y, Shibata, KI, Yamazaki, R, Shirato, H, Teduka, M & Date, H 2011, 'Radiation-Induced cancer cell repopulation: A possible mechanism implied by experiments using transplantable mouse-derived sarcoma cell line', Cell Structure and Function, vol. 36, no. 1, pp. 13-20. https://doi.org/10.1247/csf.10008
Nishioka, Takeshi ; Yasuda, Motoaki ; Takeshima, Tsuguhide ; Haga, Hisashi ; Miyai, Yusuke ; Shibata, Ken Ichiro ; Yamazaki, Rie ; Shirato, Hiroki ; Teduka, Masahiro ; Date, Hiroyuki. / Radiation-Induced cancer cell repopulation : A possible mechanism implied by experiments using transplantable mouse-derived sarcoma cell line. In: Cell Structure and Function. 2011 ; Vol. 36, No. 1. pp. 13-20.
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AU - Miyai, Yusuke

AU - Shibata, Ken Ichiro

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N2 - Purpose: Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. Materials and Methods: A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. Results: cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p<0.01, Student's t-test). Conclusions: This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.

AB - Purpose: Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. Materials and Methods: A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. Results: cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p<0.01, Student's t-test). Conclusions: This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.

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