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Glycan expression profile of signet ring cell gastric cancer cells and potential applicability of rBC2LCN-targeted lectin drug conjugate therapy. | LitMetric

AI Article Synopsis

  • Signet ring cell carcinoma (SRC) is a unique type of gastric cancer, and this study aimed to better understand its specific cell surface glycans and explore potential glycan-targeting therapies.* -
  • Researchers analyzed SRC and non-SRC cell lines using lectin microarray to identify SRC-specific glycans, finding that certain lectins had significant affinity for these glycans, particularly highlighting the importance of α2-6-linked sialic acids.* -
  • The study concluded that the rBC2LCN lectin shows promise as a therapeutic agent, demonstrating effective cancer cell targeting and inducing tumor regression in mouse models, suggesting it could serve as a new treatment option for SRC patients.*

Article 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.

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Source
http://dx.doi.org/10.1007/s10120-022-01312-xDOI Listing

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