title: Tissue transglutaminase-interleukin-6 axis facilitates peritoneal tumor spreading and metastasis of human ovarian cancer cells.
abstract: Inflammation has recently been implicated in cancer formation and progression. As tissue transglutaminase (TG2) has been associated with both inflammatory signaling and tumor cell behavior, we propose that TG2 may be an important link inducing interleukin-6 (IL-6)-mediated cancer cell aggressiveness, including cancer stem cell-like characteristics and distant hematogenous metastasis. We evaluated the effect of differential TG2 and IL-6 expression on in vivo distant metastasis of human ovarian cancer cells. IL-6 production in human ovarian cancer cells was dependent on their TG2 expression levels. The size and efficiency of tumor sphere formation were correlated with TG2 expression levels and were dependent on TG2-mediated IL-6 secretion in human ovarian cancer cells. Primary tumor growth and propagation in the peritoneum and distant hematogenous metastasis into the liver and lung were also dependent on TG2 and downstream IL-6 expression levels in human ovarian cancer cells. In this report, we provide evidence that TG2 is an important link in IL-6-mediated tumor cell aggressiveness, and that TG2 and downstream IL-6 could be important mediators of distant hematogenous metastasis of human ovarian cancer cells. Intervention specific to TG2 and/or downstream IL-6 in ovarian cancer cells could provide a promising means to control tumor metastasis.
authors.affiliation: PharmAbcine, Inc., #402 DaejeonBioventure Town, Jeonmin-dong, Yusung-gu, Daejeon, Korea.; Transplantation Research Institute, Seoul National University College of Medicine, 103 Daehakro, Jongno-gu, Seoul 110-799, Korea.
authors.forename: Keunhee
authors.initials: K
authors.lastname: Oh
authors.affiliation: Cancer Research Institute, Interdisciplinary Program of Tumor Biology, Seoul National University College of Medicine, 103 Daehakro, Jongno-gu, Seoul 110-799, Korea.; Department of Surgery, Seoul National University College of Medicine, 103 Daehakro, Jongno-gu, Seoul 110-799, Korea.
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.affiliation: Laboratory of Immunology/Cancer Biology, Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehakro, Jongno-gu, Seoul 110-799, Korea.; Cancer Research Institute, Interdisciplinary Program of Tumor Biology, Seoul National University College of Medicine, 103 Daehakro, Jongno-gu, Seoul 110-799, Korea.; Transplantation Research Institute, Seoul National University College of Medicine, 103 Daehakro, Jongno-gu, Seoul 110-799, Korea.
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Dankook University College of Medicine, 119 Dandaero, Dongnam-gu, Cheonan, Chungnam 31116, Korea.
authors.forename: Young-Bok
authors.initials: YB
authors.lastname: Yoo
keywords: Tissue transglutaminase; human ovarian cancer; interleukin-6; metastasis