Periostin promotes ovarian cancer angiogenesis and metastasis

被引:101
作者
Zhu, Min [1 ,2 ]
Fejzo, Marlena S. [2 ]
Anderson, Lee [2 ]
Dering, Judy [2 ]
Ginther, Charles [2 ]
Ramos, Lillian [2 ]
Gasson, Judith C. [2 ,3 ]
Karlan, Beth Y. [4 ,5 ]
Slamon, Dennis J. [2 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA
[5] Cedars Sinai Med Ctr, Div Gynecol Oncol, Los Angeles, CA 90048 USA
关键词
Periostin; Angiogenesis; Metastasis; Ovarian cancer; CELL-ADHESION MOLECULE; ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION; FASCICLIN-I; OSTEOBLAST; PATHWAY; DIFFERENTIATION; CARCINOMA; PATTERNS; INVASION;
D O I
10.1016/j.ygyno.2010.07.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective. Perostin (PN) has been found to be overexpressed in a variety of human malignancies including ovarian cancer. In the present study, we investigated PN expression status in a large cohort of ovarian tumors with the focus on biological influence of PN related on ovarian tumor angiogenesis and metastasis. Methods. PN expression was determined by cDNA microarray, PN northern blot and PN IHC tissue array analyses. Exogenous PN expression in ovarian cancer cells OVCAR-3 and OV2008 were achieved through retroviral transfection and confirmed by PN western blot and ELISA. The effects of exogenous PN expression on tumor angiogenesis and metastatic growth were accessed in orthotopic mouse models. The in vitro cell adhesion, migration and invasion assays were performed to investigate the potential mechanisms involved in PN's in vivo effects. Results. PN was frequently overexpressed in ovarian tumors. Higher PN levels significantly correlated with clinical late stages (III/IV) and cancer recurrence. PN was produced by engineered PN-overexpressing cells at levels comparable to that of A2780 cells, an ovarian carcinoma cell line with endogenous PN expression. PN overexpression did not change cell growth rates in vitro; however it significantly promoted intraperitoneal tumor metastatic growth in immunodeficient mice, which was associated with increased tumor angiogenesis and decreased tumor cell apoptosis. In vitro purified PN promoted cell adhesion, migration, and invasion of both human umbilical endothelial cells (HUVECs) and/or ovarian cancer cells. Conclusions. Our data indicate PN plays a critical role in both ovarian tumor angiogenesis and metastasis. Thus PN may represent a clinically effective new target for therapy of ovarian cancer. Published by Elsevier Inc.
引用
收藏
页码:337 / 344
页数:8
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