| 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.
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| ジャーナル |
Int J Mol Sci
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| 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)
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| 公開日 |
2018-10-26
|
| DOI |
10.3390/ijms19113345
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| PII |
ijms19113345
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| 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
|
| リソース情報 |
| ヒト・動物細胞 |
iPS-MEF-Ng-20D-17(APS0001) |
