Paradoxical effect of GM-CSF gene transfer on the tumorigenicity and immunogenicity of murine tumors

Jie Wang, Wen K. Yang, Yili Yang, Sung Jan Wei, Den Mei Yang, Jacqueline Whang-Peng, Yuh Min Chen, Kai Li Ting, Chou Chik Ting

Research output: Contribution to journalArticle

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Abstract

The effect of granulocyte/macrophage colony-stimulating factor (GM-CSF) gene transfer on the tumorigenicity and immunogenicity of 2 different murine tumor lines was determined. Transduction of B16 melanoma cells with the GM- CSF gene rendered the cells more immunogenic. In contrast, transduction of NG4TL4 fibrosarcoma in FVB/N mice (NG) with the GM-CSF gene showed increased tumorigenicity in a high producer line (NG-MGh). The parent NG or NG-MG cells induced the same level of cytotoxic T-lymphocyte (CTL) response and the same magnitude of tumor transplantation immunity. However, the proliferation of the NG-MGh cells was increased 2- to 10-fold. There was no increase in apoptosis in the NG cells and there was no increase of NG-MGh cells in S- phase, hence the increase of the proliferative activity appeared to be indeed inherent to the cells. Mixing the splenocytes from the NG-MGh tumor bearers with the NG tumor cells did not increase tumorigenicity but totally inhibited the growth of the NG tumor, indicating that suppressor cells were not present. Mixing 10,000 rad X-irradiated NG-MGh cells with viable NG tumor cells resulted in 3- to 10-fold increased NG tumor growth rate. The in vitro proliferation of NG cells was increased by adding both GM-CSFs and macrophages and not by either one alone, suggesting that interaction between macrophages and GM-CSFs resulted in the production of tumor growth enhancing factor(s). Our findrags suggest that trensduction of NG tumor cells with the GM-CSF gene increases tumorigenicity, which is attributed both to an increased inherent proliferative ability of the tumor cells and to the in vivo production of a tumor growth enhancing factor(s) at the tumor site.

Original languageEnglish
Pages (from-to)459-466
Number of pages8
JournalInternational Journal of Cancer
Volume75
Issue number3
DOIs
Publication statusPublished - Jan 30 1998
Externally publishedYes

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Granulocyte-Macrophage Colony-Stimulating Factor
Genes
Neoplasms
Intercellular Signaling Peptides and Proteins
Macrophages
Experimental Melanomas
Fibrosarcoma
Cytotoxic T-Lymphocytes
Growth
S Phase
Immunity
Transplantation
Cell Proliferation
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Paradoxical effect of GM-CSF gene transfer on the tumorigenicity and immunogenicity of murine tumors. / Wang, Jie; Yang, Wen K.; Yang, Yili; Wei, Sung Jan; Yang, Den Mei; Whang-Peng, Jacqueline; Chen, Yuh Min; Ting, Kai Li; Ting, Chou Chik.

In: International Journal of Cancer, Vol. 75, No. 3, 30.01.1998, p. 459-466.

Research output: Contribution to journalArticle

Wang, Jie ; Yang, Wen K. ; Yang, Yili ; Wei, Sung Jan ; Yang, Den Mei ; Whang-Peng, Jacqueline ; Chen, Yuh Min ; Ting, Kai Li ; Ting, Chou Chik. / Paradoxical effect of GM-CSF gene transfer on the tumorigenicity and immunogenicity of murine tumors. In: International Journal of Cancer. 1998 ; Vol. 75, No. 3. pp. 459-466.
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abstract = "The effect of granulocyte/macrophage colony-stimulating factor (GM-CSF) gene transfer on the tumorigenicity and immunogenicity of 2 different murine tumor lines was determined. Transduction of B16 melanoma cells with the GM- CSF gene rendered the cells more immunogenic. In contrast, transduction of NG4TL4 fibrosarcoma in FVB/N mice (NG) with the GM-CSF gene showed increased tumorigenicity in a high producer line (NG-MGh). The parent NG or NG-MG cells induced the same level of cytotoxic T-lymphocyte (CTL) response and the same magnitude of tumor transplantation immunity. However, the proliferation of the NG-MGh cells was increased 2- to 10-fold. There was no increase in apoptosis in the NG cells and there was no increase of NG-MGh cells in S- phase, hence the increase of the proliferative activity appeared to be indeed inherent to the cells. Mixing the splenocytes from the NG-MGh tumor bearers with the NG tumor cells did not increase tumorigenicity but totally inhibited the growth of the NG tumor, indicating that suppressor cells were not present. Mixing 10,000 rad X-irradiated NG-MGh cells with viable NG tumor cells resulted in 3- to 10-fold increased NG tumor growth rate. The in vitro proliferation of NG cells was increased by adding both GM-CSFs and macrophages and not by either one alone, suggesting that interaction between macrophages and GM-CSFs resulted in the production of tumor growth enhancing factor(s). Our findrags suggest that trensduction of NG tumor cells with the GM-CSF gene increases tumorigenicity, which is attributed both to an increased inherent proliferative ability of the tumor cells and to the in vivo production of a tumor growth enhancing factor(s) at the tumor site.",
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