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Surfactant protein D suppresses lung cancer progression by downregulation of epidermal growth factor signaling

Oncogene volume 34, pages 838–845 (2015)Cite this article

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A Corrigendum to this article was published on 06 August 2015

Abstract

Surfactant protein D (SP-D) is a member of the collectin family that has an important role in maintaining pulmonary homeostasis. In this study, we demonstrated that SP-D inhibited the proliferation, migration and invasion of A549 human lung adenocarcinoma cells. We found that SP-D suppressed epidermal growth factor (EGF) signaling in A549 cells, H441 human lung adenocarcinoma cells and human EGF receptor (EGFR) stable expression CHO-K1 cells. A binding study using 125I-EGF demonstrated that SP-D downregulated the binding of EGF to EGFR. A ligand blot indicated that SP-D bound to EGFR, and a lectin blot suggested that EGFR in A549 cells had both high-mannose type and complex type N-glycans. We purified the recombinant extracellular domain of EGFR (soluble EGFR=soluble EGFR (sEGFR)), and demonstrated that SP-D directly bound to sEGFR in a Ca2+-dependent manner. The binding of SP-D to sEGFR was suppressed by EDTA, mannose or N-glycopeptidase F treatment. Mass spectrometric analysis indicated that N-glycans in domain III of EGFR were of a high-mannose type. These data suggest that SP-D reduces EGF binding to EGFR through the interaction between the carbohydrate recognition domain of SP-D and N-glycans of EGFR, and downregulates EGF signaling. Our finding suggests the novel type of regulation system of EGF signaling involving lectin-to-carbohydrate interaction and downregulation of ligand binding.

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Science Research from the Japan Society for the Promotion of Science, grants from the Takeda Science Foundation and from the Suhara Foundation.

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Authors and Affiliations

  1. Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan

    Y Hasegawa, M Takahashi, S Ariki, C Nishitani, R Takamiya, A Saito, Y Uehara, J Hashimoto, Y Kurimura & Y Kuroki

  2. Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Y Hasegawa, A Saito, Y Uehara & H Takahashi

  3. Department of Molecular Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

    D Asakawa, M Tajiri & Y Wada

  4. Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, Wako, Japan

    Y Yamaguchi

  5. Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan

    J Hashimoto & Y Kurimura

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Correspondence to M Takahashi.

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Hasegawa, Y., Takahashi, M., Ariki, S. et al. Surfactant protein D suppresses lung cancer progression by downregulation of epidermal growth factor signaling. Oncogene 34, 838–845 (2015). https://doi.org/10.1038/onc.2014.20

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