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Fascin1 expression in high-grade serous ovarian carcinoma is a prognostic marker and knockdown of fascin1 suppresses the proliferation of ovarian cancer cells.

Park SH, Song JY, Kim YK, Heo JH, Kang H, Kim G, An HJ, Kim TH - Int. J. Oncol. (2013)

Bottom Line: Fascin1 overexpression was significantly correlated with lymph node involvement, distance metastasis and high International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV) (P<0.05).A Kaplan-Meier analysis showed that the fascin1 expression group was significantly associated with poor overall survival (P=0.010).We showed that inactivation of fascin1 by siRNA transfection led to a drop in cell viability, and significantly decreased tumor cell proliferation, migration and invasiveness compared to untransfected cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecologic Oncology, CHA Gangnam Medical Center, Gangnam-Gu, Seoul 135-907, Republic of Korea.

ABSTRACT
Fascin1 (FSCN1) involved in cell motility and filopodia assembly plays important roles in biological processes such as cancer invasion and metastasis of multiple epithelial tumors. High-grade serous ovarian carcinoma (HGSOC) is aggressive and metastatic by acquiring an invasive phenotype and this step requires remodeling of the actin cytoskeleton. Thus, the present study aimed to investigate the expression of fascin1 in HGSOC tissues as well as its clinical significance such as prognostic predictors and its utility of therapeutic target. Fascin1 and β-catenin were evaluated using immunohistochemistry on a tissue microarray of 79 HGSOC. Small interfering RNA (siRNA) approach was used to knock down fascin1 expression in ovarian cancer cell lines to determine whether fascin1 contributes to tumor cell proliferation, migration and invasion. Fascin1 expression levels were determined by western blot analysis after siRNA transfection using two human ovarian cancer cell lines (SKOV3 and OVCAR3). Fascin1 overexpression was significantly correlated with lymph node involvement, distance metastasis and high International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV) (P<0.05). A Kaplan-Meier analysis showed that the fascin1 expression group was significantly associated with poor overall survival (P=0.010). We showed that inactivation of fascin1 by siRNA transfection led to a drop in cell viability, and significantly decreased tumor cell proliferation, migration and invasiveness compared to untransfected cells. We found that fascin1 expression is a potential poor marker of prognosis for patients with HGSOC and knockdown of fascin1 suppresses ovarian cancer cell proliferation and migration, this could be applied for therapeutic targets in ovarian cancer treatment.

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Related in: MedlinePlus

Representative immunohistochemical analysis of the fascin1 and β-catenin expression. (A) Fascin1 was negative in the epithelial cells of the fallopian tube (negative control) and immunopositive in the endothelial cells (positive control) and (B) positive staining in cytoplasm of tumor cells of the high-grade ovarian serous carcinoma. β-catenin was observed clear membrane staining in all the cases of (C) fallopian tube and of (D) high-grade ovarian serous carcinoma.
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f1-ijo-44-03-0637: Representative immunohistochemical analysis of the fascin1 and β-catenin expression. (A) Fascin1 was negative in the epithelial cells of the fallopian tube (negative control) and immunopositive in the endothelial cells (positive control) and (B) positive staining in cytoplasm of tumor cells of the high-grade ovarian serous carcinoma. β-catenin was observed clear membrane staining in all the cases of (C) fallopian tube and of (D) high-grade ovarian serous carcinoma.

Mentions: To investigate whether fascin1 expression is related to HGSOC, we analyzed fascin1 expression in 79 HGSOC tissues. Fascin1 was immunonegative in the epithelial cells of fallopian tube as a negative control and immunopositive in the endothelial cells as a positive control (Fig. 1A). Fascin1 positive immunostained cells were those containing dark brown granules mainly distributed in the cytoplasm of HGSOC cells (Fig. 1B). This finding demonstrates upregulation of fascin1 as a phenotypic alteration in HGSOC cells. Cells with positive β-catenin expression were defined as those cells containing dark brown nuclei or cytoplasmic staining, but there is no significant β-catenin positive staining cells, whereas all cancer cells and fallopian tube epithelial cells (normal control) in this study showed membrane staining (Fig. 1C and D). Table I shows the association between fascin1 expression and clinicopathological parameters. We found that fascin1 overexpression was significantly correlated with high FIGO stage (III/IV) (P=0.021), lymph node involvement (P=0.034) and distant metastasis (P=0.040). However, fascin1 expression was not associated with other parameters such as age, and tumor recurrence.


Fascin1 expression in high-grade serous ovarian carcinoma is a prognostic marker and knockdown of fascin1 suppresses the proliferation of ovarian cancer cells.

Park SH, Song JY, Kim YK, Heo JH, Kang H, Kim G, An HJ, Kim TH - Int. J. Oncol. (2013)

Representative immunohistochemical analysis of the fascin1 and β-catenin expression. (A) Fascin1 was negative in the epithelial cells of the fallopian tube (negative control) and immunopositive in the endothelial cells (positive control) and (B) positive staining in cytoplasm of tumor cells of the high-grade ovarian serous carcinoma. β-catenin was observed clear membrane staining in all the cases of (C) fallopian tube and of (D) high-grade ovarian serous carcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928475&req=5

f1-ijo-44-03-0637: Representative immunohistochemical analysis of the fascin1 and β-catenin expression. (A) Fascin1 was negative in the epithelial cells of the fallopian tube (negative control) and immunopositive in the endothelial cells (positive control) and (B) positive staining in cytoplasm of tumor cells of the high-grade ovarian serous carcinoma. β-catenin was observed clear membrane staining in all the cases of (C) fallopian tube and of (D) high-grade ovarian serous carcinoma.
Mentions: To investigate whether fascin1 expression is related to HGSOC, we analyzed fascin1 expression in 79 HGSOC tissues. Fascin1 was immunonegative in the epithelial cells of fallopian tube as a negative control and immunopositive in the endothelial cells as a positive control (Fig. 1A). Fascin1 positive immunostained cells were those containing dark brown granules mainly distributed in the cytoplasm of HGSOC cells (Fig. 1B). This finding demonstrates upregulation of fascin1 as a phenotypic alteration in HGSOC cells. Cells with positive β-catenin expression were defined as those cells containing dark brown nuclei or cytoplasmic staining, but there is no significant β-catenin positive staining cells, whereas all cancer cells and fallopian tube epithelial cells (normal control) in this study showed membrane staining (Fig. 1C and D). Table I shows the association between fascin1 expression and clinicopathological parameters. We found that fascin1 overexpression was significantly correlated with high FIGO stage (III/IV) (P=0.021), lymph node involvement (P=0.034) and distant metastasis (P=0.040). However, fascin1 expression was not associated with other parameters such as age, and tumor recurrence.

Bottom Line: Fascin1 overexpression was significantly correlated with lymph node involvement, distance metastasis and high International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV) (P<0.05).A Kaplan-Meier analysis showed that the fascin1 expression group was significantly associated with poor overall survival (P=0.010).We showed that inactivation of fascin1 by siRNA transfection led to a drop in cell viability, and significantly decreased tumor cell proliferation, migration and invasiveness compared to untransfected cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecologic Oncology, CHA Gangnam Medical Center, Gangnam-Gu, Seoul 135-907, Republic of Korea.

ABSTRACT
Fascin1 (FSCN1) involved in cell motility and filopodia assembly plays important roles in biological processes such as cancer invasion and metastasis of multiple epithelial tumors. High-grade serous ovarian carcinoma (HGSOC) is aggressive and metastatic by acquiring an invasive phenotype and this step requires remodeling of the actin cytoskeleton. Thus, the present study aimed to investigate the expression of fascin1 in HGSOC tissues as well as its clinical significance such as prognostic predictors and its utility of therapeutic target. Fascin1 and β-catenin were evaluated using immunohistochemistry on a tissue microarray of 79 HGSOC. Small interfering RNA (siRNA) approach was used to knock down fascin1 expression in ovarian cancer cell lines to determine whether fascin1 contributes to tumor cell proliferation, migration and invasion. Fascin1 expression levels were determined by western blot analysis after siRNA transfection using two human ovarian cancer cell lines (SKOV3 and OVCAR3). Fascin1 overexpression was significantly correlated with lymph node involvement, distance metastasis and high International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV) (P<0.05). A Kaplan-Meier analysis showed that the fascin1 expression group was significantly associated with poor overall survival (P=0.010). We showed that inactivation of fascin1 by siRNA transfection led to a drop in cell viability, and significantly decreased tumor cell proliferation, migration and invasiveness compared to untransfected cells. We found that fascin1 expression is a potential poor marker of prognosis for patients with HGSOC and knockdown of fascin1 suppresses ovarian cancer cell proliferation and migration, this could be applied for therapeutic targets in ovarian cancer treatment.

Show MeSH
Related in: MedlinePlus