Limits...
Decreasing the ratio of matriptase/HAI‑1 by downregulation of matriptase as a potential adjuvant therapy in ovarian cancer.

Sun P, Jiang Z, Chen X, Xue L, Mao X, Ruan G, Song Y, Mustea A - Mol Med Rep (2016)

Bottom Line: The migration distance and number of invading HO‑8910PM cells were significantly increased compared with HO‑8910 cells.HO‑8910PM cells exhibited a significantly higher ratio of matriptase/HAI‑1 mRNA levels compared with HO‑8910 cells (0.51 vs. 0.24, ~2.2 fold increase).Similar increases in protein expression levels were also observed in HO‑8910PM cells compared with HO‑8910 cells.

View Article: PubMed Central - PubMed

Affiliation: Institute of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Children Health Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.

ABSTRACT
Tumor invasion and metastasis are complex biological processes. Matriptase and its endogenous inhibitor, hepatocyte growth factor activator inhibitor‑1 (HAI‑1) are involved in invasion and metastasis. To evaluate the ratio of matriptase/HAI‑1 and their potential therapeutic value in ovarian cancer, HO‑8910 human ovarian cancer cells and the homologous high‑metastatic HO‑8910PM cells were used as in vitro cellular models ovarian cancer. The invasive and metastatic abilities, and the expression of matriptase and HAI‑1 in these cells were detected using scratch assays, Transwell chamber assays, reverse transcription‑quantitative polymerase chain reaction, western blotting and fluorescent immunocytochemistry. Following infection with lentivirus‑mediated matriptase‑targeting small interfering RNA (siRNA), cell cycle progression and apoptosis were also analyzed. The migration distance and number of invading HO‑8910PM cells were significantly increased compared with HO‑8910 cells. HO‑8910PM cells exhibited a significantly higher ratio of matriptase/HAI‑1 mRNA levels compared with HO‑8910 cells (0.51 vs. 0.24, ~2.2 fold increase). Compared with HO‑8910 cells, the matriptase mRNA level was increased by ~3.6 fold in HO‑8910PM cells, whereas the HAI‑1 mRNA level was increased by ~1.7 fold. Similar increases in protein expression levels were also observed in HO‑8910PM cells compared with HO‑8910 cells. Migration and invasiveness were positively correlated with matriptase expression level (r=0.994, P<0.01) and the ratio of matriptase/HAI‑1 (r=0.929, P<0.01). Downregulation of matriptase using siRNA resulted in inhibition of the invasive and metastatic abilities of HO‑8910PM cells, cell cycle arrest in the G0/G1 phase and increased apoptosis. The present study demonstrated that ovarian cancer cell metastasis and invasion were more dependent on upregulation of matriptase levels than downregulation of HAI‑1. Matriptase may be a potential adjuvant therapeutic target for inhibiting ovarian cancer invasion and metastasis.

No MeSH data available.


Related in: MedlinePlus

Inhibition of the invasiveness and metastatic ability of ovarian cancer cells via matriptase suppression. (A) Invasion and (B) migration were measured by Transwell and scratch assays, respectively. Magnification, ×200. (C) The number of HO-8910PM-SI2 cells that migrated through the Transwell membrane was significantly lower (38.33±3.51) compared with HO-8910PM (100.00±4.36, P<0.01), HO-8910PM-NC (92.67±2.52, P<0.01), and HO-8910 cells (62.33±3.06, P<0.01). The number of HO-8910PM-NC cells and HO-8910PM cells that migrated through the Transwell membrane was not significantly different (P=0.185). (D) Scratch assay results indicated that matriptase depletion significantly decreased the migratory ability of HO-8910PM cells (P<0.01). Compared with that of HO-8910PM-SI2 cells (104.33±7.07 µm), the 24-h migration distances of HO-8910PM (394.08±8.20 µm, P<0.01), HO-8910PM-NC (387.44±2.76 µm, P<0.01) and HO-8910 cells (198.80±10.46 µm, P<0.01) were significantly increased. *P>0.05 vs. HO-8910PM; #P<0.05 vs. HO-8910PM. NC, negative control; SI, small interfering RNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4940087&req=5

f4-mmr-14-02-1465: Inhibition of the invasiveness and metastatic ability of ovarian cancer cells via matriptase suppression. (A) Invasion and (B) migration were measured by Transwell and scratch assays, respectively. Magnification, ×200. (C) The number of HO-8910PM-SI2 cells that migrated through the Transwell membrane was significantly lower (38.33±3.51) compared with HO-8910PM (100.00±4.36, P<0.01), HO-8910PM-NC (92.67±2.52, P<0.01), and HO-8910 cells (62.33±3.06, P<0.01). The number of HO-8910PM-NC cells and HO-8910PM cells that migrated through the Transwell membrane was not significantly different (P=0.185). (D) Scratch assay results indicated that matriptase depletion significantly decreased the migratory ability of HO-8910PM cells (P<0.01). Compared with that of HO-8910PM-SI2 cells (104.33±7.07 µm), the 24-h migration distances of HO-8910PM (394.08±8.20 µm, P<0.01), HO-8910PM-NC (387.44±2.76 µm, P<0.01) and HO-8910 cells (198.80±10.46 µm, P<0.01) were significantly increased. *P>0.05 vs. HO-8910PM; #P<0.05 vs. HO-8910PM. NC, negative control; SI, small interfering RNA.

Mentions: The invasiveness and metastatic ability of HO-8910PM-SI2 cells were compared with HO-8910PM, HO-8910PM-NC, and HO-8910 cells. The number of HO-8910PM-SI2 cells (38.33±3.51) that penetrated the Transwell chamber membrane was significantly reduced compared with HO-8910PM (100.00±4.36), HO-8910PM-NC (92.67±2.52), and HO-8910 cells (62.33±3.06, all P<0.01, Fig. 4A). Additionally, the 24-h migration distances of HO-8910PM-SI2 cells (104.33±7.07 µm) were significantly reduced compared with HO-8910PM (394.08±8.20 µm), HO-8910PM-NC (387.44±2.76 µm) and HO-8910 cells (198.80±10.46 µm; all P<0.01; Fig. 4B).


Decreasing the ratio of matriptase/HAI‑1 by downregulation of matriptase as a potential adjuvant therapy in ovarian cancer.

Sun P, Jiang Z, Chen X, Xue L, Mao X, Ruan G, Song Y, Mustea A - Mol Med Rep (2016)

Inhibition of the invasiveness and metastatic ability of ovarian cancer cells via matriptase suppression. (A) Invasion and (B) migration were measured by Transwell and scratch assays, respectively. Magnification, ×200. (C) The number of HO-8910PM-SI2 cells that migrated through the Transwell membrane was significantly lower (38.33±3.51) compared with HO-8910PM (100.00±4.36, P<0.01), HO-8910PM-NC (92.67±2.52, P<0.01), and HO-8910 cells (62.33±3.06, P<0.01). The number of HO-8910PM-NC cells and HO-8910PM cells that migrated through the Transwell membrane was not significantly different (P=0.185). (D) Scratch assay results indicated that matriptase depletion significantly decreased the migratory ability of HO-8910PM cells (P<0.01). Compared with that of HO-8910PM-SI2 cells (104.33±7.07 µm), the 24-h migration distances of HO-8910PM (394.08±8.20 µm, P<0.01), HO-8910PM-NC (387.44±2.76 µm, P<0.01) and HO-8910 cells (198.80±10.46 µm, P<0.01) were significantly increased. *P>0.05 vs. HO-8910PM; #P<0.05 vs. HO-8910PM. NC, negative control; SI, small interfering RNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940087&req=5

f4-mmr-14-02-1465: Inhibition of the invasiveness and metastatic ability of ovarian cancer cells via matriptase suppression. (A) Invasion and (B) migration were measured by Transwell and scratch assays, respectively. Magnification, ×200. (C) The number of HO-8910PM-SI2 cells that migrated through the Transwell membrane was significantly lower (38.33±3.51) compared with HO-8910PM (100.00±4.36, P<0.01), HO-8910PM-NC (92.67±2.52, P<0.01), and HO-8910 cells (62.33±3.06, P<0.01). The number of HO-8910PM-NC cells and HO-8910PM cells that migrated through the Transwell membrane was not significantly different (P=0.185). (D) Scratch assay results indicated that matriptase depletion significantly decreased the migratory ability of HO-8910PM cells (P<0.01). Compared with that of HO-8910PM-SI2 cells (104.33±7.07 µm), the 24-h migration distances of HO-8910PM (394.08±8.20 µm, P<0.01), HO-8910PM-NC (387.44±2.76 µm, P<0.01) and HO-8910 cells (198.80±10.46 µm, P<0.01) were significantly increased. *P>0.05 vs. HO-8910PM; #P<0.05 vs. HO-8910PM. NC, negative control; SI, small interfering RNA.
Mentions: The invasiveness and metastatic ability of HO-8910PM-SI2 cells were compared with HO-8910PM, HO-8910PM-NC, and HO-8910 cells. The number of HO-8910PM-SI2 cells (38.33±3.51) that penetrated the Transwell chamber membrane was significantly reduced compared with HO-8910PM (100.00±4.36), HO-8910PM-NC (92.67±2.52), and HO-8910 cells (62.33±3.06, all P<0.01, Fig. 4A). Additionally, the 24-h migration distances of HO-8910PM-SI2 cells (104.33±7.07 µm) were significantly reduced compared with HO-8910PM (394.08±8.20 µm), HO-8910PM-NC (387.44±2.76 µm) and HO-8910 cells (198.80±10.46 µm; all P<0.01; Fig. 4B).

Bottom Line: The migration distance and number of invading HO‑8910PM cells were significantly increased compared with HO‑8910 cells.HO‑8910PM cells exhibited a significantly higher ratio of matriptase/HAI‑1 mRNA levels compared with HO‑8910 cells (0.51 vs. 0.24, ~2.2 fold increase).Similar increases in protein expression levels were also observed in HO‑8910PM cells compared with HO‑8910 cells.

View Article: PubMed Central - PubMed

Affiliation: Institute of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Children Health Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.

ABSTRACT
Tumor invasion and metastasis are complex biological processes. Matriptase and its endogenous inhibitor, hepatocyte growth factor activator inhibitor‑1 (HAI‑1) are involved in invasion and metastasis. To evaluate the ratio of matriptase/HAI‑1 and their potential therapeutic value in ovarian cancer, HO‑8910 human ovarian cancer cells and the homologous high‑metastatic HO‑8910PM cells were used as in vitro cellular models ovarian cancer. The invasive and metastatic abilities, and the expression of matriptase and HAI‑1 in these cells were detected using scratch assays, Transwell chamber assays, reverse transcription‑quantitative polymerase chain reaction, western blotting and fluorescent immunocytochemistry. Following infection with lentivirus‑mediated matriptase‑targeting small interfering RNA (siRNA), cell cycle progression and apoptosis were also analyzed. The migration distance and number of invading HO‑8910PM cells were significantly increased compared with HO‑8910 cells. HO‑8910PM cells exhibited a significantly higher ratio of matriptase/HAI‑1 mRNA levels compared with HO‑8910 cells (0.51 vs. 0.24, ~2.2 fold increase). Compared with HO‑8910 cells, the matriptase mRNA level was increased by ~3.6 fold in HO‑8910PM cells, whereas the HAI‑1 mRNA level was increased by ~1.7 fold. Similar increases in protein expression levels were also observed in HO‑8910PM cells compared with HO‑8910 cells. Migration and invasiveness were positively correlated with matriptase expression level (r=0.994, P<0.01) and the ratio of matriptase/HAI‑1 (r=0.929, P<0.01). Downregulation of matriptase using siRNA resulted in inhibition of the invasive and metastatic abilities of HO‑8910PM cells, cell cycle arrest in the G0/G1 phase and increased apoptosis. The present study demonstrated that ovarian cancer cell metastasis and invasion were more dependent on upregulation of matriptase levels than downregulation of HAI‑1. Matriptase may be a potential adjuvant therapeutic target for inhibiting ovarian cancer invasion and metastasis.

No MeSH data available.


Related in: MedlinePlus