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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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The inactivation of fascin1 inhibits proliferation and invasive ability of ovarian cancer cell lines SKOV3, and OVCAR3. (A) Cell proliferation was measured by colony forming assay after fascin1 siRNA transfection. The colony formation of the transfected cells grew significantly slower than control cells at 72 h. Colony numbers of transfected cells decreased significantly to 95.7% (SKOV3), 78.1% (OVCAR3) compared with that in control cells (72 h) (P<0.05).(B) Wound-healing assays were performed to examine the effect of fascin1 inactivation on cell migration (×100). The migration activities of the transfected cells were decreased 51.3% (SKOV3), and 55.3% (OVCAR3) compared to control cells at 16 h (P<0.05). (C) Matrigel invasion assays were performed to examine the effect of fascin1 on cell invasion (×100). Diagram of the cell count in the membrane. Fascin1 siRNA transfected cells led to 35.8% (SKOV3), and 31.1% (OVCAR3) decrease in the number of invasive cells (P<0.05). The above results are from 3 independent experiments.
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f4-ijo-44-03-0637: The inactivation of fascin1 inhibits proliferation and invasive ability of ovarian cancer cell lines SKOV3, and OVCAR3. (A) Cell proliferation was measured by colony forming assay after fascin1 siRNA transfection. The colony formation of the transfected cells grew significantly slower than control cells at 72 h. Colony numbers of transfected cells decreased significantly to 95.7% (SKOV3), 78.1% (OVCAR3) compared with that in control cells (72 h) (P<0.05).(B) Wound-healing assays were performed to examine the effect of fascin1 inactivation on cell migration (×100). The migration activities of the transfected cells were decreased 51.3% (SKOV3), and 55.3% (OVCAR3) compared to control cells at 16 h (P<0.05). (C) Matrigel invasion assays were performed to examine the effect of fascin1 on cell invasion (×100). Diagram of the cell count in the membrane. Fascin1 siRNA transfected cells led to 35.8% (SKOV3), and 31.1% (OVCAR3) decrease in the number of invasive cells (P<0.05). The above results are from 3 independent experiments.

Mentions: We performed wound healing, colony forming and Matrigel invasion assays after fascin1 siRNA transfection. Colony numbers of transfected cancer cells decreased significantly to 95.7% (SKOV3), 78.1% (OVCAR3) compared with that of control cells at 72 h (P<0.05; Fig. 4A). Cell motility following wound generation showed less cell migration in transfected cells compared with that of control cells (P<0.05; Fig. 4B). After 16 h, we observed that transfected cells resulted in 51.3% (SKOV3), and 55.3% (OVCAR3) decreased migrating cell numbers in comparison with that of the control. The Matrigel invasion assay was used to assess the invasiveness of the cancer cells. The staining results are shown in Fig. 4C at 48 h. The control cells were more invasive and fascin1 siRNA transfected cells decreased significantly to 35.8% (SKOV3), 31.1% (OVCAR3) compared with that of control cells (P<0.05).


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)

The inactivation of fascin1 inhibits proliferation and invasive ability of ovarian cancer cell lines SKOV3, and OVCAR3. (A) Cell proliferation was measured by colony forming assay after fascin1 siRNA transfection. The colony formation of the transfected cells grew significantly slower than control cells at 72 h. Colony numbers of transfected cells decreased significantly to 95.7% (SKOV3), 78.1% (OVCAR3) compared with that in control cells (72 h) (P<0.05).(B) Wound-healing assays were performed to examine the effect of fascin1 inactivation on cell migration (×100). The migration activities of the transfected cells were decreased 51.3% (SKOV3), and 55.3% (OVCAR3) compared to control cells at 16 h (P<0.05). (C) Matrigel invasion assays were performed to examine the effect of fascin1 on cell invasion (×100). Diagram of the cell count in the membrane. Fascin1 siRNA transfected cells led to 35.8% (SKOV3), and 31.1% (OVCAR3) decrease in the number of invasive cells (P<0.05). The above results are from 3 independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-ijo-44-03-0637: The inactivation of fascin1 inhibits proliferation and invasive ability of ovarian cancer cell lines SKOV3, and OVCAR3. (A) Cell proliferation was measured by colony forming assay after fascin1 siRNA transfection. The colony formation of the transfected cells grew significantly slower than control cells at 72 h. Colony numbers of transfected cells decreased significantly to 95.7% (SKOV3), 78.1% (OVCAR3) compared with that in control cells (72 h) (P<0.05).(B) Wound-healing assays were performed to examine the effect of fascin1 inactivation on cell migration (×100). The migration activities of the transfected cells were decreased 51.3% (SKOV3), and 55.3% (OVCAR3) compared to control cells at 16 h (P<0.05). (C) Matrigel invasion assays were performed to examine the effect of fascin1 on cell invasion (×100). Diagram of the cell count in the membrane. Fascin1 siRNA transfected cells led to 35.8% (SKOV3), and 31.1% (OVCAR3) decrease in the number of invasive cells (P<0.05). The above results are from 3 independent experiments.
Mentions: We performed wound healing, colony forming and Matrigel invasion assays after fascin1 siRNA transfection. Colony numbers of transfected cancer cells decreased significantly to 95.7% (SKOV3), 78.1% (OVCAR3) compared with that of control cells at 72 h (P<0.05; Fig. 4A). Cell motility following wound generation showed less cell migration in transfected cells compared with that of control cells (P<0.05; Fig. 4B). After 16 h, we observed that transfected cells resulted in 51.3% (SKOV3), and 55.3% (OVCAR3) decreased migrating cell numbers in comparison with that of the control. The Matrigel invasion assay was used to assess the invasiveness of the cancer cells. The staining results are shown in Fig. 4C at 48 h. The control cells were more invasive and fascin1 siRNA transfected cells decreased significantly to 35.8% (SKOV3), 31.1% (OVCAR3) compared with that of control cells (P<0.05).

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