TY - JOUR
T1 - SPARC was overexpressed in human endometrial cancer stem-like cells and promoted migration activity
AU - Yusuf, Nurismangul
AU - Inagaki, Tetsunori
AU - Kusunoki, Soshi
AU - Okabe, Hitomi
AU - Yamada, Izumi
AU - Matsumoto, Akemi
AU - Terao, Yasuhisa
AU - Takeda, Satoru
AU - Kato, Kiyoko
N1 - Funding Information:
We thank the Laboratory of Molecular and Biochemical Reseach, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan, for technical assistance. This work was supported by grants-in aid ( 23390392 ) and ( 24659736 ) from the Ministry of Education, Culture, Sports, Science and Technology, Japan .
PY - 2014/8
Y1 - 2014/8
N2 - Objectives We previously demonstrated that side-population (SP) cells found in human endometrial cancer tissue have features of cancer stem cells (CSCs). Endometrial cancer SP cells show enhanced migration, the potential to differentiate into the mesenchymal cell lineage, and they are associated with the epithelial-mesenchymal transition (EMT). In this study, we analyzed the expression and function of a specific protein, SPARC (secreted protein acidic and rich in cysteine) which we found to be up-regulated in endometrial cancer. Methods We performed microarray expression analysis to screen for up-regulated genes in CSCs using a set of RK12V-SP cells and -non-SP (NSP) cells. We used the MetaCore package to identify the Gene GO pathway MAPs associated with the up-regulated genes. Here, we investigated the expression and functions of SPARC, one of the genes up-regulated in endometrial CSCs. We established SPARC-overexpressing cells by transfecting endometrial cancer cells (Ishikawa cells [IK-SPARC cells]). We characterized these cells' growth rate, tumorigenicity, migration and invasion activity. The levels and locations of SPARC protein expression in Hec1SP cells-derived tumors and endometrial cancer tissues were examined by immunohistochemistry. Results SPARC was detected by microarray expression analysis during screens for up-regulated genes in SP and NSP CSC. The level of SPARC expression was enhanced in Hec1 SP cells compared with that in Hec1 non-SP cells. SPARC enhanced fibronectin expression and promoted migration activity in IK cells. SPARC expression suppressed tumor growth but promoted formation of tumor stroma. SPARC was expressed in endometrial cancer tissues, in particular, poorly differentiated endometrioid adenocarcinoma, clear and serous adenocarcinoma,but not in normal endometrial tissue. Conclusion This is the first report of overexpression of SPARC in endometrial cancer stem-like cells. SPARC expression is associated with cell migration and stroma formation.
AB - Objectives We previously demonstrated that side-population (SP) cells found in human endometrial cancer tissue have features of cancer stem cells (CSCs). Endometrial cancer SP cells show enhanced migration, the potential to differentiate into the mesenchymal cell lineage, and they are associated with the epithelial-mesenchymal transition (EMT). In this study, we analyzed the expression and function of a specific protein, SPARC (secreted protein acidic and rich in cysteine) which we found to be up-regulated in endometrial cancer. Methods We performed microarray expression analysis to screen for up-regulated genes in CSCs using a set of RK12V-SP cells and -non-SP (NSP) cells. We used the MetaCore package to identify the Gene GO pathway MAPs associated with the up-regulated genes. Here, we investigated the expression and functions of SPARC, one of the genes up-regulated in endometrial CSCs. We established SPARC-overexpressing cells by transfecting endometrial cancer cells (Ishikawa cells [IK-SPARC cells]). We characterized these cells' growth rate, tumorigenicity, migration and invasion activity. The levels and locations of SPARC protein expression in Hec1SP cells-derived tumors and endometrial cancer tissues were examined by immunohistochemistry. Results SPARC was detected by microarray expression analysis during screens for up-regulated genes in SP and NSP CSC. The level of SPARC expression was enhanced in Hec1 SP cells compared with that in Hec1 non-SP cells. SPARC enhanced fibronectin expression and promoted migration activity in IK cells. SPARC expression suppressed tumor growth but promoted formation of tumor stroma. SPARC was expressed in endometrial cancer tissues, in particular, poorly differentiated endometrioid adenocarcinoma, clear and serous adenocarcinoma,but not in normal endometrial tissue. Conclusion This is the first report of overexpression of SPARC in endometrial cancer stem-like cells. SPARC expression is associated with cell migration and stroma formation.
UR - http://www.scopus.com/inward/record.url?scp=84905593649&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905593649&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2014.04.009
DO - 10.1016/j.ygyno.2014.04.009
M3 - Article
C2 - 24769035
AN - SCOPUS:84905593649
SN - 0090-8258
VL - 134
SP - 356
EP - 363
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -
