title: Decreasing the ratio of matriptase/HAI‑1 by downregulation of matriptase as a potential adjuvant therapy in ovarian cancer.
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.
authors.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.
authors.forename: Pengming
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.
authors.forename: Zhongqing
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Chen
authors.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.
authors.forename: Lifang
authors.initials: L
authors.lastname: Xue
authors.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.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Mao
authors.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.
authors.forename: Guanyu
authors.initials: G
authors.lastname: Ruan
authors.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.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Song
authors.affiliation: Gynecological Tumor Center, Department of Obstetrics and Gynecology, Medical University Greifswald, D‑17475 Greifswald, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mustea
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C109149:SPINT1 protein, human; D012697:Serine Endopeptidases; C485595:matriptase