2009年3月3日
Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells
Proceedings of the National Academy of Sciences of the United States of America
- 巻
- 106
- 号
- 9
- 開始ページ
- 3095
- 終了ページ
- 3100
- DOI
- 10.1073/pnas.0810110106
Cell surfaces of epithelial cancer are covered by complex carbohydrates, whose structures function in malignancy and metastasis. However, the mechanism underlying carbohydrate-dependent cancer metastasis has not been defined. Previously, we identified a carbohydrate-mimicry peptide designated I-peptide, which inhibits carbohydrate-dependent lung colonization of sialyl Lewis X-expressing B16-FTIII-M cells in E/P-selectin doubly-deficient mice. We hypothesized that lung endothelial cells express an unknown carbohydrate receptor, designated as I-peptide receptor (IPR), responsible for lung colonization of B16-FTIII-M cells. Here, we visualized IPR by in vivo biotinylation, which revealed that the major IPR is a group of 35-kDa proteins. IPR proteins isolated by I-peptide affinity chromatography were identified by proteomics as Ser/Arg-rich alternative pre-mRNA splicing factors or Sfrs1, Sfrs2, Sfrs5, and Sfrs7 gene products. Bacterially expressed Sfrs1 protein bound to B16-FTIII-M cells but not to parental B16 cells. Recombinant Sfrs1 protein bound to a series of fucosylated oligosaccharides in glycan array and plate-binding assays. When anti-Sfrs antibodies were injected intravenously into mice, antibodies labeled a subset of lung capillaries. Anti-Sfrs antibodies inhibited homing of I-peptide-displaying phage to the lung colonization of B16-FTIII-M cells in vivo in the mouse. These results strongly suggest that Sfrs proteins are responsible for fucosylated carbohydrate-dependent lung metastasis of epithelial cancers.
- リンク情報
-
- DOI
- https://doi.org/10.1073/pnas.0810110106
- CiNii Articles
- http://ci.nii.ac.jp/naid/80020186144
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/19218444
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=62649162330&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=62649162330&origin=inward
- ID情報
-
- DOI : 10.1073/pnas.0810110106
- ISSN : 0027-8424
- eISSN : 1091-6490
- CiNii Articles ID : 80020186144
- PubMed ID : 19218444
- SCOPUS ID : 62649162330