Therapeutic adenoviral gene transfer of a glycosyltransferase for prevention of peritoneal dissemination and metastasis of gastric cancer

Y. I. Kawamura, Y. Adachi, D. T. Curiel, R. Kawashima, R. Kannagi, N. Nishimoto, T. Dohi

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Increased expression of sialyl Lewis x/a carbohydrates, ligands for E-selectin, correlates with clinically advanced stages and metastasis of gastric and colon cancers. In contrast, Sd a carbohydrate is abundantly detected in the normal gastrointestinal mucosa but dramatically reduced or lost in cancer tissues. A glycosyltransferase, β1,4N-acetylgalactosaminyltransferase 2 (B4GALNT2) that catalyzes Sd a carbohydrate synthesis, is silenced in cancer. In the present study, we aimed at reducing the expression of sialyl Lewis x/a of cancer cells in vivo by forced expression of B4GALNT2 and Sd a, thereby preventing dissemination/metastasis, especially metastasis triggered by surgical maneuvers. We used a fiber-modified adenovirus (Ad) vector that contained a chimeric construct with a serotype 5 shaft and a serotype 3 knob. Using this Ad5/3 vector, we successfully introduced the B4GALNT2 gene into a human gastric cancer cell line KATO III in vitro and confirmed replacement of sialyl Lewis x to Sd a with a decrease in E-selectin-dependent adhesion. Administration of Ad5/3-B4GALNT2 vectors into the peritoneal cavity of mice after inoculation of KATO III cells with laparotomy significantly reduced the incidence of metastasis. Our results indicate that the transfer of a single gene encoding B4GALNT2 modified carbohydrate chains of cancer cells in vivo and decreased tumor dissemination and metastasis.

Original languageEnglish
Pages (from-to)427-433
Number of pages7
JournalCancer gene therapy
Volume21
Issue number10
DOIs
StatePublished - Oct 25 2014

Fingerprint

Dive into the research topics of 'Therapeutic adenoviral gene transfer of a glycosyltransferase for prevention of peritoneal dissemination and metastasis of gastric cancer'. Together they form a unique fingerprint.

Cite this