A role for PI3K-Akt signaling in pulmonary metastatic nodule formation of the osteosarcoma cell line, LM8

  • Authors: Yasushi Fukaya, Naoki Ishiguro, Takeshi Senga, Yasukatsu Ichigotani, Yasuyoshi Sohara, Motomu Tsutsui, Tomone Shioura, Takashi Iwamoto, Michinari Hamaguchi
  • View Affiliations

  • Published online on: Saturday, October 1, 2005
  • Pages: 847-852
  • DOI: 10.3892/or.14.4.847

Abstract

To search for the intracellular signaling pathway critical for the pulmonary metastasis of osteosarcoma, we examined two osteosarcoma cell lines with different metastatic capability, Dunn and LM8. While parental Dunn is poorly metastatic to lung, LM8, derived from Dunn by in vivo selection through pulmonary metastasis, displays clear capability of pulmonary metastasis. We found that LM8 had higher levels of Akt phosphorylation and Ezrin expression than Dunn. In contrast, no clear difference was observed between Dunn and LM8 in other signaling mediators, including MAPK, SAPK and Stat3. In contrast to Dunn, LM8 secreted higher levels of matrix metalloproteinase-2 and -9, showed higher levels of invasiveness and cell motility, and displayed strong pulmonary metastasis. Inhibition of PI3K-Akt signaling in LM8 by a PI3K inhibitor, LY294002, or by a dominant negative form of Akt, resulted in suppression of MMP secretion, in vitro invasiveness, cell locomotion and in vivo pulmonary metastasis. In contrast, expression of an active form of Akt in Dunn substantially activated its MMP secretion, in vitro invasiveness, cell locomotion and in vivo pulmonary metastasis. Taken together, our results demonstrate, for the first time, an important role of Akt signaling in pulmonary metastasis of osteosarcoma.
Journal Cover

October 2005
Volume 14 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

2012 Impact Factor: 2.297
Ranked #36/196 Oncology
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APA
Fukaya, Y., Ishiguro, N., Senga, T., Ichigotani, Y., Sohara, Y., Tsutsui, M., Shioura, T., Iwamoto, T., & Hamaguchi, M. (2005). A role for PI3K-Akt signaling in pulmonary metastatic nodule formation of the osteosarcoma cell line, LM8. Oncology Reports, 14(4), 847-852.
MLA
Fukaya, Ishiguro, Senga, Ichigotani, Sohara, Tsutsui, Shioura, Iwamoto, and Michinari Hamaguchi. "A role for PI3K-Akt signaling in pulmonary metastatic nodule formation of the osteosarcoma cell line, LM8." Oncology Reports Oncology Reports 14.4 (2005): 847-852.
Chicago
Fukaya, Ishiguro, Senga, Ichigotani, Sohara, Tsutsui, Shioura, Iwamoto, and Michinari Hamaguchi. "A role for PI3K-Akt signaling in pulmonary metastatic nodule formation of the osteosarcoma cell line, LM8." Oncology Reports Oncology Reports 14 no. 4 (2005): 847-852.