RRC ID 65857
著者 Harada E, Serada S, Fujimoto M, Takahashi Y, Takahashi T, Hara H, Nakatsuka R, Sugase T, Nishigaki T, Saito Y, Hiramatsu K, Nojima S, Mitsuo R, Ohkawara T, Morii E, Mori M, Doki Y, Kaneda Y, Naka T.
タイトル Glypican-1 targeted antibody-based therapy induces preclinical antitumor activity against esophageal squamous cell carcinoma.
ジャーナル Oncotarget
Abstract Esophageal squamous cell carcinoma (ESCC) has a poor prognosis despite the development of multimodal therapy. Expression of glypican-1 (GPC1) has been reported to be elevated in a subset of patients with ESCC and associated with chemoresistance. This study aimed to determine the association of GPC1 with ESCC growth and potential usefulness of the GPC1 targeted therapy by monoclonal antibody (mAb) in ESCC. Expression of GPC1 was higher in ESCC tumor tissues than in adjacent non-tumoral tissues and normal tissues. Knockdown of GPC1 decreased growth of ESCC cells and induced apoptosis via inhibition of EGFR, AKT and p44/42-MAPK signaling pathways in vitro. Anti-GPC1 mAb strongly inhibited tumor growth via antibody-dependent cellular cytotoxicity dependent and independent manner in GPC1-positive ESCC xenograft models. Anti-GPC1 mAb also inhibited tumor growth of GPC1 positive ESCC patients derived tumor xenograft models. Furthermore, anti-GPC1 mAb showed a significant tumor growth inhibition with decreased angiogenesis compared with IgG treated controls in ESCC xenografted mice. Treatment with anti-GPC1 mAb was not toxic in mice. Anti-GPC1 mAb may have a potent anti-tumor effect and represent a novel treatment option for patients with GPC1-positive ESCC.
巻・号 8(15)
ページ 24741-24752
公開日 2017-4-11
DOI 10.18632/oncotarget.15799
PII 15799
PMID 28445969
PMC PMC5421884
MeSH Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Proliferation Esophageal Neoplasms / genetics* Esophageal Neoplasms / pathology Esophageal Squamous Cell Carcinoma Female Glypicans / metabolism* Humans Male Transfection
IF 5.168
リソース情報
ヒト・動物細胞 TE-8(RCB2098) TE-11(RCB2100) TE-14(RCB2101)