Evidence of dual function of macrophage migration inhibitory factor relevant to tumor progression and regression

  • Authors:
    • Tsuyoshi Fukushima
    • Jun Nishihira
    • Takashi Yoshiki
    • Kazuya Iwabuchi
    • Chikako Iwabuchi
    • Yoshiki Yamasaki
    • Masao Kondo
    • Bailong Sun
    • Yuji Sato
    • Satoru Todo
  • View Affiliations

  • Published online on: July 1, 2005     https://doi.org/10.3892/ijmm.16.1.119
  • Pages: 119-126
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Abstract

Macrophage migration inhibitory factor (MIF) is known to play an important role in broad-spectrum inflammation and immune responses. To evaluate the role of MIF in tumor growth, we established transgenic (Tg) mice (ICR strain) driven by cytomegalovirus (CMV) enhancer and β-actin promoter. We inoculated Tg mice in the back with murine sarcoma cell line S-180 cells. The tumor growth rate was more enhanced in Tg mice than in littermate non-Tg mice up to day 9 after tumor inoculation. Surprisingly, most tumors embedded on the back of Tg mice regressed at day 10 after inoculation and eventually disappeared. Tumor volumes of non-Tg mice incessantly increased until death. We reinoculated the Tg mice with S-180 cells, which had been recovered from the first challenge, and found that the tumor cells were completely rejected in all cases. To identify the effector cells that eradicated the tumor cells, we prepared spleen cells from tumor-bearing Tg mice and carried out cell lysis assay. The magnitude of cytolytic activity of spleen cells obtained from Tg mice was significantly higher against S-180 cells, as well as natural killer cell-sensitive YAC-1 cells, than was the activity of cells from non-Tg mice. Furthermore, we observed that CTL activity of Tg mice against S-180 cells was significantly decreased by the deletion of CD8+ T cells or NK cells. On the other hand, the deletion of CD4+ cells minimally affected the cytolytic activity. Taken together, these results suggest that MIF has the potential to promote tumor growth and angiogenesis in the early phase and, by contrast, this protein could activate CD8+ cytotoxic T cells and NK cells, leading to tumor regression.

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July 2005
Volume 16 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Fukushima T, Nishihira J, Yoshiki T, Iwabuchi K, Iwabuchi C, Yamasaki Y, Kondo M, Sun B, Sato Y, Todo S, Todo S, et al: Evidence of dual function of macrophage migration inhibitory factor relevant to tumor progression and regression. Int J Mol Med 16: 119-126, 2005.
APA
Fukushima, T., Nishihira, J., Yoshiki, T., Iwabuchi, K., Iwabuchi, C., Yamasaki, Y. ... Todo, S. (2005). Evidence of dual function of macrophage migration inhibitory factor relevant to tumor progression and regression. International Journal of Molecular Medicine, 16, 119-126. https://doi.org/10.3892/ijmm.16.1.119
MLA
Fukushima, T., Nishihira, J., Yoshiki, T., Iwabuchi, K., Iwabuchi, C., Yamasaki, Y., Kondo, M., Sun, B., Sato, Y., Todo, S."Evidence of dual function of macrophage migration inhibitory factor relevant to tumor progression and regression". International Journal of Molecular Medicine 16.1 (2005): 119-126.
Chicago
Fukushima, T., Nishihira, J., Yoshiki, T., Iwabuchi, K., Iwabuchi, C., Yamasaki, Y., Kondo, M., Sun, B., Sato, Y., Todo, S."Evidence of dual function of macrophage migration inhibitory factor relevant to tumor progression and regression". International Journal of Molecular Medicine 16, no. 1 (2005): 119-126. https://doi.org/10.3892/ijmm.16.1.119