Induction of macrophage migration inhibitory factor by lysophosphatidic acid: Relevance to tumor growth and angiogenesis

  • Authors:
    • Bailong Sun
    • Jun Nishihira
    • Masaki Suzuki
    • Nobuyuki Fukushima
    • Teruo Ishibashi
    • Masao Kondo
    • Yuji Sato
    • Satoru Todo
  • View Affiliations

  • Published online on: October 1, 2003     https://doi.org/10.3892/ijmm.12.4.633
  • Pages: 633-641
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Abstract

Macrophage migration inhibitory factor (MIF) plays an important role not only in the immune system, but also in tumorigenesis. Lysophosphatidic acid (LPA), a unique lipid mediator, shares several biological functions with MIF, including promotion of tumor cell growth and associated angiogenesis. In this study, we investigated the signaling cross-talk between these two molecules during tumorigenesis and angiogenesis. We first examined the expression of MIF mRNA on a murine colon cancer cell line, colon 26, by LPA. We found that LPA enhanced the expression of MIF mRNA in a dose-dependent manner in vitro. In parallel, LPA stimulated cell growth and up-regulated the vascular endothelial growth factor (VEGF). These effects were dramatically blocked by 21 base double strand (ds) RNA specific for mouse MIF mRNA (RNAi). In vivo, colon 26 cells treated with MIF dsRNA were injected into the backs of mice. The size of tumor volumes became significantly smaller than that of controls. Angiogenesis examined by a Millipore chamber method was also suppressed by the MIF dsRNA. Next, we evaluated the signal transduction pathway relevant to the mitogen-activated protein kinase (MAPK) and Akt/PI3K pathways in response to LPA by RNAi. Ras activation and phosphorylation of Akt and ERK1/2 were strongly suppressed by the dsRNA. On the other hand, tyrosine phosphorylation was minimally changed by the treatment. Taken together, these results suggest that MIF could promote both tumor cell growth and angiogenesis induced by LPA via both the Ras-MAPK and Ras-Akt/PI3K signaling pathways.

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October 2003
Volume 12 Issue 4

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

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Spandidos Publications style
Sun B, Nishihira J, Suzuki M, Fukushima N, Ishibashi T, Kondo M, Sato Y and Todo S: Induction of macrophage migration inhibitory factor by lysophosphatidic acid: Relevance to tumor growth and angiogenesis. Int J Mol Med 12: 633-641, 2003
APA
Sun, B., Nishihira, J., Suzuki, M., Fukushima, N., Ishibashi, T., Kondo, M. ... Todo, S. (2003). Induction of macrophage migration inhibitory factor by lysophosphatidic acid: Relevance to tumor growth and angiogenesis. International Journal of Molecular Medicine, 12, 633-641. https://doi.org/10.3892/ijmm.12.4.633
MLA
Sun, B., Nishihira, J., Suzuki, M., Fukushima, N., Ishibashi, T., Kondo, M., Sato, Y., Todo, S."Induction of macrophage migration inhibitory factor by lysophosphatidic acid: Relevance to tumor growth and angiogenesis". International Journal of Molecular Medicine 12.4 (2003): 633-641.
Chicago
Sun, B., Nishihira, J., Suzuki, M., Fukushima, N., Ishibashi, T., Kondo, M., Sato, Y., Todo, S."Induction of macrophage migration inhibitory factor by lysophosphatidic acid: Relevance to tumor growth and angiogenesis". International Journal of Molecular Medicine 12, no. 4 (2003): 633-641. https://doi.org/10.3892/ijmm.12.4.633