論文 - 詳細
| RRC ID | 87895 |
|---|---|
| 著者 | Yang Y, Akashi Y, Shimomura O, Tateno H, Saito S, Hiemori K, Miyazaki Y, Furuta T, Kitaguchi D, Kuroda Y, Pakavarin L, Oda T. |
| タイトル | Glycan expression profile of signet ring cell gastric cancer cells and potential applicability of rBC2LCN-targeted lectin drug conjugate therapy. |
| ジャーナル | Gastric Cancer |
| Abstract |
BACKGROUND:Signet ring cell carcinoma (SRC) is a distinct subtype of gastric cancer (GC); however, the specific characteristics of cancer cell surface glycans and glycosylation remain unclear. In this study, we investigated SRC-specific glycans using lectin microarray and evaluated the potential applicability of a glycan-targeting therapy. METHODS:SRC cell lines (NUGC-4 and KATO-III) and non-SRC (NSRC) cell lines (NCI-N87, SNU-1, and MKN-45) were subjected to lectin microarray analysis to identify the SRC-specific glycans. Additionally, we performed immunohistochemical lectin staining and evaluated the anti-tumor effects of lectin drug conjugates (LDCs) using high-affinity lectins for SRC. RESULTS:Among the 96 lectins tested, 11 high-affinity and 8 low-affinity lectins were identified for SRC. Glycan-binding motifs varied in the high-affinity lectins, but 5 (62.5%) low-affinity lectins bound the same glycan structure, α2-6-linked sialic acids. The ratio of signal intensity in SRC to NSRC (SRC/NSRC) was highest in the rBC2LCN lectin (1.930-fold), followed by the BPL lectin (1.786-fold). rBC2LCN lectin showed high affinity for both SRC cell lines and one of the three NSRC cell lines (NCI-N87). The therapeutic effects of the LDC, rBC2LCN-PE38 (rBC2LCN, and Pseudomonas exotoxin A), showed cytocidal effects in vitro and tumor regression in in vivo mouse xenograft models. CONCLUSION:We reported specific glycan profiles in SRC cells, showing reduced α2-6-linked sialic acids. Additionally, we found a targeted therapy using rBC2LCN lectin might be applicable as an alternative treatment option for patients with SRC. |
| 巻・号 | 25(5) |
| ページ | 896-905 |
| 公開日 | 2022-9-1 |
| DOI | 10.1007/s10120-022-01312-x |
| PII | 10.1007/s10120-022-01312-x |
| PMID | 35715659 |
| MeSH | Animals Carcinoma, Signet Ring Cell* / drug therapy Carcinoma, Signet Ring Cell* / pathology Humans Lectins / metabolism Lectins / therapeutic use Mice Polysaccharides / metabolism Polysaccharides / pharmacology Sialic Acids Stomach Neoplasms* / pathology |
| リソース情報 | |
| ヒト・動物細胞 | NUGC-4(RCB1939) |