[Effects of chemokine receptor and its ligand on migration of ovarian cancer cells].
OBJECTIVE
Chemokine receptors express on many tumor cells, and closely correlate with migration and metastasis of tumor cells. This study was to investigate expressions of chemokine(C-X-C) receptor 4 (CXCR4) and chemokine (C-X-C motif) ligand 12 (CXCL12) in human ovarian epithelial tumor cells, and their effects on migration of tumor cells.


METHODS
Expression of CXCR4 mRNA and protein in 15 specimens of epithelial ovarian cancer tissue, ovarian cancer cell line CAOV3, endothelial cell line HUVEC, and 10 specimens of normal ovary tissue were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. Expression of CXCL12 mRNA in retroperitoneal lymph nodes, and smooth muscle of fallopian tube from the same 15 epithelial ovarian cancer patients was tested by RT-PCR, quantity of CXCL12 in ascites of 15 patients was assayed using ELISA. Boyden Transwells was used to analyze effects of CXCL12, and cancerous ascites on chemotaxis of CAOV3, and HUVEC cells.


RESULTS
(1) Expression levels of CXCR4 mRNA in ovary cancer tissues, CAOV3 cells, and HUVEC cells were 2.30+/-1.12, 1.89+/-1.20, and 1.68+/-1.11, respectively; those of CXCR4 protein were 1.35+/-0.14, 1.86+/-0.34, and 1.96+/-0.23, respectively; CXCR4 mRNA and protein can't be detected in normal ovarian tissues. (2) In 15 ovarian cancer patients, concentrations of CXCL12 in ascites were 632-9 326 pg/ml, and CXCL12 mRNA level in retroperitoneal lymph nodes was 1.14+/-0.87, CXCL12 mRNA can't be detected in smooth muscle of fallopian tube. (3) Recombinant human CXCL12 induced migration of CAOV3, and HUVEC cells, the chemotactic indices (CI) were 3.9+/-1.2, and 4.1+/-1.6, significantly higher than those of control (1.0+/-0.4, and 1.1+/-0.7) (P<0.05)u cancerous ascites induced migration of CAOV3 cells with CI of 1.9+/-0.8, significantly higher than that of control (P<0.05).


CONCLUSIONS
CXCR4 and CXCL12 may play roles in metastasis of epithelial ovarian cancer by promoting migration of tumor cells and endothelial cells.
Li
Fang
F
Department of Obstetrics and Gynecology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430-030, P.R. China.
Zhu
Huai-Shi
HS
Han
Zhi-Qiang
ZQ
Chen
Gang
G
Gao
Qing-Lei
QL
Jia
Ping
P
Zhang
A-Li
AL
Xi
Ling
L
Xu
Qian
Q
Liao
Guo-Ning
GN
Wang
Shi-Xuan
SX
Lu
Yun-Ping
YP
Ma
Ding
D
D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002633:Chemotaxis; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012333:RNA, Messenger; D019718:Receptors, CXCR4