論文 - 詳細
| RRC ID | 67143 |
|---|---|
| 著者 | Alam MJ, Takahashi R, Afify SM, Oo AKK, Kumon K, Nawara HM, Khayrani AC, Du J, Zahra MH, Seno A, Salomon DS, Seno M. |
| タイトル | Exogenous Cripto-1 Suppresses Self-Renewal of Cancer Stem Cell Model. |
| ジャーナル | Int J Mol Sci |
| Abstract |
Cripto-1 is a glycophosphatidylinositol (GPI) anchored signaling protein of epidermal growth factor (EGF)-Cripto-1-FRL1-Cryptic (CFC) family and plays a significant role in the early developmental stages and in the different types of cancer cells, epithelial to mesenchymal transition and tumor angiogenesis. Previously, we have developed cancer stem cells (miPS-LLCcm) from mouse iPSCs by culturing them in the presence of conditioned medium of Lewis Lung Carcinoma (LLC) cells for four weeks. Nodal and Cripto-1 were confirmed to be expressed in miPS-LLCcm cells by quantitative reverse transcription PCR (rt-qPCR) implying that Cr-1 was required in maintaining stemness. To investigate the biological effect of adding exogenous soluble CR-1 to the cancer stem cells, we have prepared a C-terminally truncated soluble form of recombinant human CR-1 protein (rhsfCR-1), in which the GPI anchored moiety was removed by substitution of a stop codon through site-directed mutagenesis. rhsfCR-1 effectively suppressed the proliferation and sphere forming ability of miPS-LLCcm cells in a dose-dependent manner in the range of 0 to 5 µg/mL, due to the suppression of Nodal-Cripto-1/ALK4/Smad2 signaling pathway. Frequency of sphere-forming cells was dropped from 1/40 to 1/69 by rhsfCR-1 at 1 µg/mL. Moreover, rhsfCR-1 in the range of 0 to 1 µg/mL also limited the differentiation of miPS-LLCcm cells into vascular endothelial cells probably due to the suppression of self-renewal, which should reduce the number of cells with stemness property. As demonstrated by a soluble form of exogenous Cripto-1 in this study, the efficient blockade would be an attractive way to study Cripto-1 dependent cancer stem cell properties for therapeutic application. |
| 巻・号 | 19(11) |
| 公開日 | 2018-10-26 |
| DOI | 10.3390/ijms19113345 |
| PII | ijms19113345 |
| PMID | 30373174 |
| PMC | PMC6274844 |
| MeSH | Animals Cell Differentiation Cell Line Cell Self Renewal* GPI-Linked Proteins / metabolism* Humans Intercellular Signaling Peptides and Proteins / metabolism* Mice Neoplasm Proteins / metabolism* Neoplasms / metabolism Neoplastic Stem Cells / cytology* Neoplastic Stem Cells / metabolism Recombinant Proteins / metabolism Signal Transduction Smad2 Protein / metabolism |
| IF | 4.556 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | iPS-MEF-Ng-20D-17(APS0001) |