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Aerosol delivery of lentivirus-mediated O-glycosylation mutant osteopontin suppresses lung tumorigenesis in K-ras LA1 mice

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Abstract

Background

Osteopontin (OPN) is a secreted glycophosphoprotein that has been implicated in the regulation of cancer development. The function of OPN is primarily regulated through post-translational modification such as glycosylation. As yet, however, the relationship between OPN glycosylation and lung cancer development has not been investigated. In this study, we addressed this issue by studying the effect of a triple mutant (TM) of OPN, which is mutated at three O-glycosylation sites, on lung cancer development in K-ras LA1 mice, a murine model for human non-small cell lung cancer.

Methods

Aerosolized lentivirus-based OPN TM was delivered into the lungs of K-ras LA1 mice using a nose-only-inhalation chamber 3 times/wk for 4 wks. Subsequently, the effects of repeated delivery of OPN TM on lung tumorigenesis and its concomitant OPN-mediated signaling pathways were investigated.

Results

Aerosol-delivered OPN TM inhibited lung tumorigenesis. In addition, the OPN-mediated Akt signaling pathway was inhibited. OPN TM also decreased NF-κB activity and the phosphorylation of 4E-BP1, while facilitating apoptosis in the lungs of K-ras LA1 mice.

Conclusions

Our results show that aerosol delivery of OPN TM successfully suppresses lung cancer development in the K-ras LA1 mouse model and, therefore, warrant its further investigation as a possible therapeutic strategy for non-small cell lung cancer.

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Acknowledgments

This work was supported by a National Research Foundation of Korea Grant funded by the Korean Government (MEST) (NRF-2012-0000102) and partially supported by the Research Institute for Veterinary Science, Seoul National University. MHC acknowledges the support from the Veterinary Research Institute of Seoul National University, Korea.

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The authors have no conflict of interest.

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Author notes

  1. Soon-Kyung Hwang

    Present address: Gene Regulation Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA

  2. Hu-Lin Jiang

    Present address: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China

Authors and Affiliations

  1. Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea

    Arash Minai-Tehrani, Seung-Hee Chang, Jung-Taek Kwon, Soon-Kyung Hwang, Ji-Eun Kim, Ji-Young Shin, Kyeong-Nam Yu, Sung-Jin Park, Hu-Lin Jiang, Ji-Hye Kim, Seong-Ho Hong, Bitna Kang & Myung-Haing Cho

  2. Department of Nanofusion Technology, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 151-742, South Korea

    Ji-Eun Kim, Ji-Hye Kim & Myung-Haing Cho

  3. Graduate Group of Tumor Biology, Seoul National University, Seoul, 151-742, South Korea

    Myung-Haing Cho

  4. Advanced Institute of Convergence Technology, Seoul National University, Suwon, 443-270, South Korea

    Myung-Haing Cho

  5. Department of Pathology, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea

    Duyeoul Kim & Chan-Hee Chae

  6. Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul, 139-706, South Korea

    Kee-Ho Lee

  7. Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA, 30322, USA

    George R. Beck Jr

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  1. Arash Minai-Tehrani
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Minai-Tehrani, A., Chang, SH., Kwon, JT. et al. Aerosol delivery of lentivirus-mediated O-glycosylation mutant osteopontin suppresses lung tumorigenesis in K-ras LA1 mice. Cell Oncol. 36, 15–26 (2013). https://doi.org/10.1007/s13402-012-0107-3

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