Internalization of REIC/Dkk-3 protein by induced pluripotent stem cell-derived embryoid bodies and extra-embryonic tissues

  • Authors:
    • Ken Kataoka
    • Masakiyo Sakaguchi
    • Kun Peng Li
    • Chika Taketa
    • Ken-Ichi Yamamoto
    • Gang Du
    • Hiroaki Funahashi
    • Hitoshi Murata
    • Nam-Ho Huh
  • View Affiliations

  • Published online on: December 1, 2010     https://doi.org/10.3892/ijmm_00000534
  • Pages: 853-859
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Abstract

REIC/Dkk-3 was first identified as a down-regulated gene in a number of human immortalized cells and human tumor-derived cell lines. Overexpression of the REIC/Dkk-3 gene using an adenovirus vector (Ad-REIC) has showed a potent selective therapeutic effect on various human cancers through induction of ER stress. Furthermore, we recently showed that Ad-REIC has an indirect host-mediated anti-tumor activity by induction of IL-7. However, the physiological function of REIC/Dkk-3 is still unclear. As a first step to study the possible receptor(s) for secreted REIC/Dkk-3, we analyzed the internalization of Cy3-labeled recombinant REIC/Dkk-3 protein. Among the cell lines screened, mouse induced pluripotent stem (iPS) cells showed a unique pattern of internalization. The internalization was observed in peripheral cells of spherical colonies formed spontaneously, but not in undifferentiated iPS cells. When we analyzed embryoid bodies (EBs) derived from iPS cells, REIC/Dkk-3 protein was internalized specifically by differentiated cells located at the periphery of EBs. Interestingly, Dkk-1 was internalized by undifferentiated cells at the center of the EBs. When developmental tissue was analyzed, internalization of REIC/Dkk-3 protein was strictly limited to extra-embryonic tissue, such as the trophectoderm layer of 4.5 days post-coitus (dpc) blastocysts and the chorionic membrane at 16.5 dpc. The mechanism of the internalization was confirmed to be endocytosis. These findings will contribute to knowledge on the interaction of REIC/Dkk-3 with a possible receptor(s).

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December 2010
Volume 26 Issue 6

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

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Spandidos Publications style
Kataoka K, Sakaguchi M, Li KP, Taketa C, Yamamoto K, Du G, Funahashi H, Murata H and Huh N: Internalization of REIC/Dkk-3 protein by induced pluripotent stem cell-derived embryoid bodies and extra-embryonic tissues . Int J Mol Med 26: 853-859, 2010
APA
Kataoka, K., Sakaguchi, M., Li, K.P., Taketa, C., Yamamoto, K., Du, G. ... Huh, N. (2010). Internalization of REIC/Dkk-3 protein by induced pluripotent stem cell-derived embryoid bodies and extra-embryonic tissues . International Journal of Molecular Medicine, 26, 853-859. https://doi.org/10.3892/ijmm_00000534
MLA
Kataoka, K., Sakaguchi, M., Li, K. P., Taketa, C., Yamamoto, K., Du, G., Funahashi, H., Murata, H., Huh, N."Internalization of REIC/Dkk-3 protein by induced pluripotent stem cell-derived embryoid bodies and extra-embryonic tissues ". International Journal of Molecular Medicine 26.6 (2010): 853-859.
Chicago
Kataoka, K., Sakaguchi, M., Li, K. P., Taketa, C., Yamamoto, K., Du, G., Funahashi, H., Murata, H., Huh, N."Internalization of REIC/Dkk-3 protein by induced pluripotent stem cell-derived embryoid bodies and extra-embryonic tissues ". International Journal of Molecular Medicine 26, no. 6 (2010): 853-859. https://doi.org/10.3892/ijmm_00000534