Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit

Molecular Cancer Therapeutics
Philipp Emanuel GeyerKlaus-Peter Janssen

Abstract

The B-subunit of the bacterial Shiga toxin (STxB), which is nontoxic and has low immunogenicity, can be used for tumor targeting of breast, colon, and pancreatic cancer. Here, we tested whether human gastric cancers, which are among the most aggressive tumor entities, express the cellular receptor of Shiga toxin, the glycosphingolipid globotriaosylceramide (Gb3/CD77). The majority of cases showed an extensive staining for Gb3 (36/50 cases, 72%), as evidenced on tissue sections of surgically resected specimen. Gb3 expression was detected independent of type (diffuse/intestinal), and was negatively correlated to increasing tumor-node-metastasis stages (P = 0.0385), as well as with markers for senescence. Gb3 expression in nondiseased gastric mucosa was restricted to chief and parietal cells at the bottom of the gastric glands, and was not elevated in endoscopic samples of gastritis (n = 10). Gb3 expression in established cell lines of gastric carcinoma was heterogeneous, with 6 of 10 lines being positive, evidenced by flow cytometry. STxB was taken up rapidly by live Gb3-positive gastric cancer cells, following the intracellular retrograde transport route, avoiding lysosomes and rapidly reaching the Golgi apparatus and the endopl...Continue Reading

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Citations

Mar 10, 2020·International Journal of Cancer. Journal International Du Cancer·Fabian C FrankeKlaus-Peter Janssen
Dec 19, 2018·Journal of Cell Science·Domenico RussoGiovanni D'Angelo
Apr 22, 2020·Cancer Metastasis Reviews·Tore SkotlandKirsten Sandvig
Jan 19, 2021·The Journal of Biological Chemistry·Katarzyna Szymczak-KulusMarcin Czerwinski
Jan 28, 2021·Microorganisms·Tina Vida PlavecAleš Berlec
Mar 24, 2021·European Journal of Pharmacology·Zeinab MohseniAbbas Ali Imani Fooladi
Jun 3, 2021·Toxins·Clifford Lingwood
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ludger Johannes
May 13, 2021·Glycobiology·Krzysztof MikolajczykMarcin Czerwinski
Apr 27, 2019·ACS Chemical Biology·Nadine Eliane SchmitOliver Hantschel

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