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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

Expression of matriptase and HAI-1 in HO-8910 and HO-8910PM ovarian cancer cells was detected 24 h after the infection with lentivirus. (A) The relative mRNA levels of matriptase and HAI-1 were higher in HO-8910PM cells compared with HO-8910 cells as detected by reverse transcription-quantitative polymerase chain reaction. Matriptase mRNA level was ~3.6-fold higher in HO-8910PM, while HAI-1 mRNA was ~1.7-fold higher compared with HO-8910 cells. (B) The matriptase protein was primarily detected in the cytoplasm of ovarian cancer cells. Magnification, ×400. A stronger intensity green staining was observed in HO-8920PM cells compared to HO-8910 cells. Under ×400 magnification, the average intensity of the green signal was significantly higher in HO-8910PM compared with HO-8910 cells (15.63±0.83 vs. 7.65±1.30, t=8.959, P=0.001, ~2-fold). (C) Matriptase protein expression was higher in HO-8910PM compared with HO-8910 cells as detected by western blotting. Matriptase protein levels were increased 2.3-fold in HO-8910PM, while HAI-1 protein levels increased ~1.2-fold, compared with HO-8910 cells. There was a 1.9-fold increase in matriptase/HAI-1 mRNA expression ratio in HO-8910PM cells (0.51) compared with HO-8910 cells (0.24). #P<0.05 vs. HO-8910. HAI-1, hepatocyte growth factor activator inhibitor-1.
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f2-mmr-14-02-1465: Expression of matriptase and HAI-1 in HO-8910 and HO-8910PM ovarian cancer cells was detected 24 h after the infection with lentivirus. (A) The relative mRNA levels of matriptase and HAI-1 were higher in HO-8910PM cells compared with HO-8910 cells as detected by reverse transcription-quantitative polymerase chain reaction. Matriptase mRNA level was ~3.6-fold higher in HO-8910PM, while HAI-1 mRNA was ~1.7-fold higher compared with HO-8910 cells. (B) The matriptase protein was primarily detected in the cytoplasm of ovarian cancer cells. Magnification, ×400. A stronger intensity green staining was observed in HO-8920PM cells compared to HO-8910 cells. Under ×400 magnification, the average intensity of the green signal was significantly higher in HO-8910PM compared with HO-8910 cells (15.63±0.83 vs. 7.65±1.30, t=8.959, P=0.001, ~2-fold). (C) Matriptase protein expression was higher in HO-8910PM compared with HO-8910 cells as detected by western blotting. Matriptase protein levels were increased 2.3-fold in HO-8910PM, while HAI-1 protein levels increased ~1.2-fold, compared with HO-8910 cells. There was a 1.9-fold increase in matriptase/HAI-1 mRNA expression ratio in HO-8910PM cells (0.51) compared with HO-8910 cells (0.24). #P<0.05 vs. HO-8910. HAI-1, hepatocyte growth factor activator inhibitor-1.

Mentions: The mRNA expression levels of matriptase and HAI-1 were higher in HO-8910PM cells compared with HO-8910 cells (0.446±0.03 vs. 0.124±0.03, P<0.01 and 0.863±0.03 vs. 0.519±0.03, P<0.01, respectively; Fig. 2A) as measured by RT-qPCR. The mRNA level of matriptase was increased by ~3.6 fold and the mRNA level of HAI-1 was increased by ~1.7 fold in HO-8910PM compared with HO-8910 cells. The mRNA ratio of matriptase/HAI-1 was increased from 0.24 in HO-8910 cells to 0.52 in HO-8910PM (P<0.01; ~2.2 fold increase). Immunocytochemistry demonstrated that the matriptase protein is predominantly localized in the cytoplasm and at the cell membrane (Fig. 2B). Additionally, compared with HO-8910 cells, stronger signal intensity (15.63±0.83 vs. 7.65±1.30; P<0.01; Fig. 2B) and higher protein expression levels of matriptase and HAI-1 (0.25±0.13 vs. 0.11±0.02, and 0.54±0.16 vs. 0.46±0.12; P<0.01; Fig 2C) were detected in HO-8910PM cells. The protein level of HAI-1 was increased by ~2.3 fold in HO-8910PM compared with HO-8910 cells, and the protein of HAI-1 was increased by ~1.2 fold. The protein ratio of matriptase/HAI-1 was increased from 0.24 in HO-8910 cells to 0.47 in HO-8910PM cells (~1.9 fold increase).


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)

Expression of matriptase and HAI-1 in HO-8910 and HO-8910PM ovarian cancer cells was detected 24 h after the infection with lentivirus. (A) The relative mRNA levels of matriptase and HAI-1 were higher in HO-8910PM cells compared with HO-8910 cells as detected by reverse transcription-quantitative polymerase chain reaction. Matriptase mRNA level was ~3.6-fold higher in HO-8910PM, while HAI-1 mRNA was ~1.7-fold higher compared with HO-8910 cells. (B) The matriptase protein was primarily detected in the cytoplasm of ovarian cancer cells. Magnification, ×400. A stronger intensity green staining was observed in HO-8920PM cells compared to HO-8910 cells. Under ×400 magnification, the average intensity of the green signal was significantly higher in HO-8910PM compared with HO-8910 cells (15.63±0.83 vs. 7.65±1.30, t=8.959, P=0.001, ~2-fold). (C) Matriptase protein expression was higher in HO-8910PM compared with HO-8910 cells as detected by western blotting. Matriptase protein levels were increased 2.3-fold in HO-8910PM, while HAI-1 protein levels increased ~1.2-fold, compared with HO-8910 cells. There was a 1.9-fold increase in matriptase/HAI-1 mRNA expression ratio in HO-8910PM cells (0.51) compared with HO-8910 cells (0.24). #P<0.05 vs. HO-8910. HAI-1, hepatocyte growth factor activator inhibitor-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-mmr-14-02-1465: Expression of matriptase and HAI-1 in HO-8910 and HO-8910PM ovarian cancer cells was detected 24 h after the infection with lentivirus. (A) The relative mRNA levels of matriptase and HAI-1 were higher in HO-8910PM cells compared with HO-8910 cells as detected by reverse transcription-quantitative polymerase chain reaction. Matriptase mRNA level was ~3.6-fold higher in HO-8910PM, while HAI-1 mRNA was ~1.7-fold higher compared with HO-8910 cells. (B) The matriptase protein was primarily detected in the cytoplasm of ovarian cancer cells. Magnification, ×400. A stronger intensity green staining was observed in HO-8920PM cells compared to HO-8910 cells. Under ×400 magnification, the average intensity of the green signal was significantly higher in HO-8910PM compared with HO-8910 cells (15.63±0.83 vs. 7.65±1.30, t=8.959, P=0.001, ~2-fold). (C) Matriptase protein expression was higher in HO-8910PM compared with HO-8910 cells as detected by western blotting. Matriptase protein levels were increased 2.3-fold in HO-8910PM, while HAI-1 protein levels increased ~1.2-fold, compared with HO-8910 cells. There was a 1.9-fold increase in matriptase/HAI-1 mRNA expression ratio in HO-8910PM cells (0.51) compared with HO-8910 cells (0.24). #P<0.05 vs. HO-8910. HAI-1, hepatocyte growth factor activator inhibitor-1.
Mentions: The mRNA expression levels of matriptase and HAI-1 were higher in HO-8910PM cells compared with HO-8910 cells (0.446±0.03 vs. 0.124±0.03, P<0.01 and 0.863±0.03 vs. 0.519±0.03, P<0.01, respectively; Fig. 2A) as measured by RT-qPCR. The mRNA level of matriptase was increased by ~3.6 fold and the mRNA level of HAI-1 was increased by ~1.7 fold in HO-8910PM compared with HO-8910 cells. The mRNA ratio of matriptase/HAI-1 was increased from 0.24 in HO-8910 cells to 0.52 in HO-8910PM (P<0.01; ~2.2 fold increase). Immunocytochemistry demonstrated that the matriptase protein is predominantly localized in the cytoplasm and at the cell membrane (Fig. 2B). Additionally, compared with HO-8910 cells, stronger signal intensity (15.63±0.83 vs. 7.65±1.30; P<0.01; Fig. 2B) and higher protein expression levels of matriptase and HAI-1 (0.25±0.13 vs. 0.11±0.02, and 0.54±0.16 vs. 0.46±0.12; P<0.01; Fig 2C) were detected in HO-8910PM cells. The protein level of HAI-1 was increased by ~2.3 fold in HO-8910PM compared with HO-8910 cells, and the protein of HAI-1 was increased by ~1.2 fold. The protein ratio of matriptase/HAI-1 was increased from 0.24 in HO-8910 cells to 0.47 in HO-8910PM cells (~1.9 fold increase).

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