Inhibition of osteopontin suppresses in vitro and in vivo angiogenesis in endometrial cancer.
OBJECTIVE
Osteopontin (OPN) has been found to play an important role in tumor angiogenesis in recent years. Our previous studies have shown that OPN is overexpressed in tumor-associated human endometrial endothelial cells (HEECs) isolated from tissue samples of patients with endometrial cancer. In the present study, we aimed to further determine the role of OPN in endometrial cancer-associated angiogenesis.


METHODS
We knock down OPN expression in HEECs and human endometrial cancer Ishikawa (ISK) cells using the small interference RNA method, and then evaluate the effects of OPN on endometrial cancer-associated angiogenesis by in vivo mouse studies and in vitro assays.


RESULTS
Our results revealed that proliferative activity of HEECs and ISK cells in vitro was not affected by transfection with the siOPN-RNA (P>0.05). Inhibition of OPN expression in HEECs reduced the cell migration, with the percentage of repaired area of 36.32+/-2.88 vs. 8.54+/-1.13 (P=0.007). HEEC/siOPN and ISK/siOPN demonstrated 67.4% and 51.2% decreased invasiveness compared with controls, respectively (P<0.05). The number of branched points per well was obviously lower in HEEC/siOPN than that in HEEC/Control (32.46+/-17.10 vs. 53.15+/-15.44, P=0.021). Furthermore, ISK cells transfected with OPN siRNA formed smaller tumor in mice and led to a lower microvessel density, i.e., angiogenesis, in transplanted tumors of mice than scrambled siRNA controls (12.88+/-7.14 vs. 28.42+/-9.69 vessels per HPF, P=0.019).


CONCLUSIONS
These data confirm the positive role of OPN in endometrial cancer-associated angiogenesis and might be of great benefit for finding rational approach in endometrial cancer therapy.
Du
Xue-lian
XL
Department of Gynecologic Oncology, Shandong Cancer Hospital & Institute, Jinan 250117, PR China.
Jiang
Tao
T
Sheng
Xiu-gui
XG
Gao
Rong
R
Li
Qing-shui
QS
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D016889:Endometrial Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D053495:Osteopontin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; D053495:Osteopontin