Synergistic antitumor interaction of human monocyte chemotactant protein-1 gene transfer and modulator for tumor-infiltrating macrophages

Emi Nakashima, Yuri Kubota, Ryo Matsushita, Eijiro Ozaki, Fujio Ichimura, Sakae Kawahara, Isao Nakanishi, Kouji Kuno, Kouji Matsushima

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose. In order to evaluate the possibility of synergistic antitumor gene therapy by the gene delivery of monocyte chemotactant protein-1 (MCP- 1/MCAF/IE), the effect of a biological response modulater for macrophages on tumor progression of gene transfected tumor cells was studied. Methods. Cachexia-inducing adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid or MCP-1 cDNA. Results. The production of MCP-1 reached 70-80 ng/ml in vitro when transfectant cells were cultured at a cell density of 1 x 105 cells/ml for 3 days. Transfection of MCP-1 cDNA did not affect the growth rate in vitro. Also, MCP-1-transfectants formed tumors after intra-footpad inoculation similar in size to the parental cells. The number of infiltrating macrophages in the primary tumor of the transfectant rapidly increased from the 3rd to 5th day after inoculation as revealed by immunohistochemical staining using an antibody against mouse macrophages. An earlier, greater, but no longer-lasting increase in tumor- infiltrating macrophages was induced in tumors by MCP-1 transfection was compared to that induced by the parent cells. On the 10th day after the inoculation, the tumor-infiltrating macrophages in mice inoculated MCP-1 transfectants were decreased to a level similar to that of the parent cells. Groups of mice were treated intraperitoneally with LPS at different times after the inoculation. Tumor cells producing high levels of MCP-1 were significantly lysed by macrophages treated with LPS, whereas parental or control transfected cells were not. Conclusions. Combination immunotherapy can provide a rationale for the application of MCP-1 treatment to increase immunological responses to cancer.

Original languageEnglish
Pages (from-to)685-689
Number of pages5
JournalPharmaceutical Research
Volume15
Issue number5
DOIs
Publication statusPublished - 1998

Fingerprint

Gene transfer
Macrophages
Modulators
Tumors
Monocytes
Neoplasms
Proteins
Cells
Transfection
Complementary DNA
Genes
Gene therapy
Cachexia
Genetic Therapy
Immunotherapy
Plasmids
Cultured Cells
Colon
Adenocarcinoma
Clone Cells

Keywords

  • Biological response modulater
  • Chemokine
  • Colon 26
  • Gene transfer
  • Monocyte chemotactic and activating factor

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Synergistic antitumor interaction of human monocyte chemotactant protein-1 gene transfer and modulator for tumor-infiltrating macrophages. / Nakashima, Emi; Kubota, Yuri; Matsushita, Ryo; Ozaki, Eijiro; Ichimura, Fujio; Kawahara, Sakae; Nakanishi, Isao; Kuno, Kouji; Matsushima, Kouji.

In: Pharmaceutical Research, Vol. 15, No. 5, 1998, p. 685-689.

Research output: Contribution to journalArticle

Nakashima, E, Kubota, Y, Matsushita, R, Ozaki, E, Ichimura, F, Kawahara, S, Nakanishi, I, Kuno, K & Matsushima, K 1998, 'Synergistic antitumor interaction of human monocyte chemotactant protein-1 gene transfer and modulator for tumor-infiltrating macrophages', Pharmaceutical Research, vol. 15, no. 5, pp. 685-689. https://doi.org/10.1023/A:1011906600304
Nakashima, Emi ; Kubota, Yuri ; Matsushita, Ryo ; Ozaki, Eijiro ; Ichimura, Fujio ; Kawahara, Sakae ; Nakanishi, Isao ; Kuno, Kouji ; Matsushima, Kouji. / Synergistic antitumor interaction of human monocyte chemotactant protein-1 gene transfer and modulator for tumor-infiltrating macrophages. In: Pharmaceutical Research. 1998 ; Vol. 15, No. 5. pp. 685-689.
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AU - Nakashima, Emi

AU - Kubota, Yuri

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AU - Ozaki, Eijiro

AU - Ichimura, Fujio

AU - Kawahara, Sakae

AU - Nakanishi, Isao

AU - Kuno, Kouji

AU - Matsushima, Kouji

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N2 - Purpose. In order to evaluate the possibility of synergistic antitumor gene therapy by the gene delivery of monocyte chemotactant protein-1 (MCP- 1/MCAF/IE), the effect of a biological response modulater for macrophages on tumor progression of gene transfected tumor cells was studied. Methods. Cachexia-inducing adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid or MCP-1 cDNA. Results. The production of MCP-1 reached 70-80 ng/ml in vitro when transfectant cells were cultured at a cell density of 1 x 105 cells/ml for 3 days. Transfection of MCP-1 cDNA did not affect the growth rate in vitro. Also, MCP-1-transfectants formed tumors after intra-footpad inoculation similar in size to the parental cells. The number of infiltrating macrophages in the primary tumor of the transfectant rapidly increased from the 3rd to 5th day after inoculation as revealed by immunohistochemical staining using an antibody against mouse macrophages. An earlier, greater, but no longer-lasting increase in tumor- infiltrating macrophages was induced in tumors by MCP-1 transfection was compared to that induced by the parent cells. On the 10th day after the inoculation, the tumor-infiltrating macrophages in mice inoculated MCP-1 transfectants were decreased to a level similar to that of the parent cells. Groups of mice were treated intraperitoneally with LPS at different times after the inoculation. Tumor cells producing high levels of MCP-1 were significantly lysed by macrophages treated with LPS, whereas parental or control transfected cells were not. Conclusions. Combination immunotherapy can provide a rationale for the application of MCP-1 treatment to increase immunological responses to cancer.

AB - Purpose. In order to evaluate the possibility of synergistic antitumor gene therapy by the gene delivery of monocyte chemotactant protein-1 (MCP- 1/MCAF/IE), the effect of a biological response modulater for macrophages on tumor progression of gene transfected tumor cells was studied. Methods. Cachexia-inducing adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid or MCP-1 cDNA. Results. The production of MCP-1 reached 70-80 ng/ml in vitro when transfectant cells were cultured at a cell density of 1 x 105 cells/ml for 3 days. Transfection of MCP-1 cDNA did not affect the growth rate in vitro. Also, MCP-1-transfectants formed tumors after intra-footpad inoculation similar in size to the parental cells. The number of infiltrating macrophages in the primary tumor of the transfectant rapidly increased from the 3rd to 5th day after inoculation as revealed by immunohistochemical staining using an antibody against mouse macrophages. An earlier, greater, but no longer-lasting increase in tumor- infiltrating macrophages was induced in tumors by MCP-1 transfection was compared to that induced by the parent cells. On the 10th day after the inoculation, the tumor-infiltrating macrophages in mice inoculated MCP-1 transfectants were decreased to a level similar to that of the parent cells. Groups of mice were treated intraperitoneally with LPS at different times after the inoculation. Tumor cells producing high levels of MCP-1 were significantly lysed by macrophages treated with LPS, whereas parental or control transfected cells were not. Conclusions. Combination immunotherapy can provide a rationale for the application of MCP-1 treatment to increase immunological responses to cancer.

KW - Biological response modulater

KW - Chemokine

KW - Colon 26

KW - Gene transfer

KW - Monocyte chemotactic and activating factor

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