Open AccessSuppression of gastric cancer dissemination by ephrin‐B1‐derived peptide
Author(s) -
Tanaka Masamitsu,
Kamata Reiko,
Yanagihara Kazuyoshi,
Sakai Ryuichi
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01352.x
Subject(s) - erythropoietin producing hepatocellular (eph) receptor , ephrin , dishevelled , cancer research , cancer cell , rhoa , biology , tyrosine kinase , signal transducing adaptor protein , cancer , receptor tyrosine kinase , signal transduction , microbiology and biotechnology , wnt signaling pathway , frizzled , genetics
Interaction of the Eph family of receptor protein tyrosine kinases and their ligands, ephrin family members, induces bidirectional signaling through cell–cell contacts. High expression of B‐type ephrin is associated with high invasion potential of tumors, and we previously observed that signaling through the C‐terminus of ephrin‐B1 mediates the migration and invasion of cells, and is involved in the promotion of carcinomatous peritonitis in vivo . Here we show that the intracellular introduction of a synthetic peptide derived from ephrin‐B1 C‐terminus blocks ephrin‐B1 mediated signaling in scirrhous gastric cancer cells. Treatment of cancer cells with a fusion peptide consisting of HIV‐TAT and amino acids 331–346 of ephrin‐B1 (PTD‐EFNB1‐C) suppressed the activation of RhoA, mediated by the association of ephrin‐B1 with an adaptor protein Dishevelled, and also inhibited extracellular secretion of metalloproteinase. Moreover, injection of PTD‐EFNB1‐C peptide into the peritoneal cavity of nude mice suppressed carcinomatous peritonitis of intraperitoneally transplanted scirrhous gastric cancer cells. These results indicate the possible application of ephrin‐B1 C‐terminal peptide to develop novel protein therapy for scirrhous gastric carcinoma, especially in the stage of tumor progression, including peritoneal dissemination. ( Cancer Sci 2009)