Ecto-5'-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells.
OBJECTIVE
Associated with many molecules, metastasis includes cell adhesion to extracellular matrix, migration towards specific direction and invasion into local vessel of distant organs. The purpose of the present study was to evaluate the role of ecto-5'-nucleotidase (eN, ecto-5-NT, CD73) generated extracellular adenosine in biologically malignant behaviors of human breast cancer cell lines.


METHODS
Two human breast cancer cell lines, T-47D with lower expression of CD73 and MB-MDA-231 with higher expression of CD73, were used to investigate the functions of CD73. The effects of CD73 over-expression on invasion, migration and adhesion were observed in T-47D transfected with pcDNA-NT5E plasmid. The effects of specific CD73 inhibitor, alpha, ss-methylene ADP (APCP), were observed in MB-MDA-231 cells.


RESULTS
The results showed CD-73 overexpression increased invasion, migration and adhesion to ECM of the pcDNA-NT5E transfected T-47D cells compared to the saline and mock vector controls. The increased cell mobility of CD-73-overexpressed T-47D cells was blocked by APCP. Adenosine increased the mobility of wild type T-47D cells. APCP inhibited the mobility of the MB-MDA-231 cells.


CONCLUSIONS
Taken together, our results indicated that CD73 may facilitate the adhesion, migration and invasion of human breast cancer cells through its enzyme activity of generating adenosine. This study provided a possibly molecular mechanism of metastasis of breast carcinoma.
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, 138# Yixueyuan Road, Shanghai 200032, People's Republic of China.
Li
L
Wang
Xuerui
X
Zhou
Tingting
T
Zhou
Dong
D
Ma
Sifeng
S
Chen
Xiuling
X
Zhi
Lianhua
L
Yin
Zhimin
Z
Shao
Zhouluo
Z
Ou
Ping
P
Zhou
D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000241:Adenosine / Q000096:biosynthesis; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D014162:Transfection
C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D000244:Adenosine Diphosphate; D015720:5'-Nucleotidase; D000241:Adenosine