Periostin promotes ovarian cancer angiogenesis and metastasis.
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.
Zhu
Min
M
Division of Hematology-Oncology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. MZhu@mednet.ucla.edu
Fejzo
Marlena S
MS
Anderson
Lee
L
Dering
Judy
J
Ginther
Charles
C
Ramos
Lillian
L
Gasson
Judith C
JC
Karlan
Beth Y
BY
Slamon
Dennis J
DJ
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D015815:Cell Adhesion Molecules; C512835:POSTN protein, human