SPARC was overexpressed in human endometrial cancer stem-like cells and promoted migration activity

Nurismangul Yusuf, Tetsunori Inagaki, Soshi Kusunoki, Hitomi Okabe, Izumi Yamada, Akemi Matsumoto, Yasuhisa Terao, Satoru Takeda, Kiyoko Kato

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)356-363
Number of pages8
JournalGynecologic Oncology
Volume134
Issue number2
DOIs
Publication statusPublished - Jan 1 2014

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Neoplastic Stem Cells
Endometrial Neoplasms
Cell Movement
Cysteine
Side-Population Cells
Proteins
Genes
Microarray Analysis
Population
Endometrioid Carcinoma
Neoplasms
Epithelial-Mesenchymal Transition
Cell Lineage
Growth
Fibronectins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynaecology

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SPARC was overexpressed in human endometrial cancer stem-like cells and promoted migration activity. / Yusuf, Nurismangul; Inagaki, Tetsunori; Kusunoki, Soshi; Okabe, Hitomi; Yamada, Izumi; Matsumoto, Akemi; Terao, Yasuhisa; Takeda, Satoru; Kato, Kiyoko.

In: Gynecologic Oncology, Vol. 134, No. 2, 01.01.2014, p. 356-363.

Research output: Contribution to journalArticle

Yusuf, N, Inagaki, T, Kusunoki, S, Okabe, H, Yamada, I, Matsumoto, A, Terao, Y, Takeda, S & Kato, K 2014, 'SPARC was overexpressed in human endometrial cancer stem-like cells and promoted migration activity', Gynecologic Oncology, vol. 134, no. 2, pp. 356-363. https://doi.org/10.1016/j.ygyno.2014.04.009
Yusuf, Nurismangul ; Inagaki, Tetsunori ; Kusunoki, Soshi ; Okabe, Hitomi ; Yamada, Izumi ; Matsumoto, Akemi ; Terao, Yasuhisa ; Takeda, Satoru ; Kato, Kiyoko. / SPARC was overexpressed in human endometrial cancer stem-like cells and promoted migration activity. In: Gynecologic Oncology. 2014 ; Vol. 134, No. 2. pp. 356-363.
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abstract = "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.",
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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

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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.

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