Cathepsin L is involved in proliferation and invasion of ovarian cancer cells

Zhang,Luosheng; Wei,Lixia; Shen,Guanzhu; He,Benfu; Gong,Wei; Min,Na; Zhang,Li; Duan,Yuxin; Xie,Jingran; Luo,Huiyan; Gao,Xingwang

doi:10.3892/mmr.2014.2706

Cathepsin L is involved in proliferation and invasion of ovarian cancer cells

Authors:
- Luosheng Zhang
- Lixia Wei
- Guanzhu Shen
- Benfu He
- Wei Gong
- Na Min
- Li Zhang
- Yuxin Duan
- Jingran Xie
- Huiyan Luo
- Xingwang Gao
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Affiliations: Department of Oncology, The 458th Hospital of PLA, Guangzhou, Guangdong 510602, P.R. China, Department of Oncology, Sun Yat‑sen University Cancer Center, Guangzhou, Guangdong 510000, P.R. China, Department of Oncology, The 421th Hospital of PLA, Guangzhou, Guangdong 510000, P.R. China
Published online on: October 20, 2014 https://doi.org/10.3892/mmr.2014.2706
Pages: 468-474

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Abstract

Cathepsin L (CTSL) is a lysosomal cysteine protease that has been found to be overexpressed in ovarian cancer (OC). The aim of the present study was to investigate the possible involvement of CTSL in the development of OC. In this study, RNA interference with a CTSL small hairpin RNA (CTSL‑shRNA), and a plasmid carrying CTSL were used to identify the effects of this enzyme on the regulation of the malignant behavior of OC cells. OV‑90 and SKOV3 human ovarian cancer cell lines were selected as cell models in vitro and in vivo. The results showed that downregulation of CTSL significantly inhibits the proliferative and invasive capability of SKOV3 cells, and that upregulation of CTSL in OV‑90 cells leads to opposite effects. Compared with parental OC cells, cells in which CTSL was silenced exhibited a reduced capacity to develop into tumors in nude mice, while the growth of tumor xenografts derived from these cells was markedly constrained. In conclusion, the results suggested that CTSL contributes to the proliferation and metastasis of OC, and that CTSL may be a novel molecular target for OC treatment.

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1	American Cancer Society. Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society; 2014 Last accessed May 21, 2014
2	Su Z, Graybill WS and Zhu Y: Detection and monitoring of ovarian cancer. Clin Chim Acta. 415:341–345. 2013. View Article : Google Scholar : PubMed/NCBI
3	Turk V, Stoka V, Vasiljeva O, et al: Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim Biophys Acta. 1824:68–88. 2012. View Article : Google Scholar : PubMed/NCBI
4	Gocheva V and Joyce JA: Cysteine cathepsins and the cutting edge of cancer invasion. Cell Cycle. 6:60–64. 2007. View Article : Google Scholar : PubMed/NCBI
5	Mason SD and Joyce JA: Proteolytic networks in cancer. Trends Cell Biol. 21:228–237. 2011. View Article : Google Scholar : PubMed/NCBI
6	Conus S and Simon HU: Cathepsins and their involvement in immune responses. Swiss Med Wkly. 140:w130422010.PubMed/NCBI
7	Krepela E: Cysteine proteinases in tumor cell growth and apoptosis. Neoplasma. 48:332–349. 2001.PubMed/NCBI
8	Mohamed MM and Sloane BF: Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer. 6:764–775. 2006. View Article : Google Scholar : PubMed/NCBI
9	Duffy MJ: The role of proteolytic enzymes in cancer invasion and metastasis. Clin Exp Metastasis. 10:145–155. 1992. View Article : Google Scholar : PubMed/NCBI
10	Mullins SR, Sameni M, Blum G, Bogyo M, Sloane BF and Moin K: Three-dimensional cultures modeling premalignant progression of human breast epithelial cells: role of cysteine cathepsins. Biol Chem. 393:1405–1416. 2012. View Article : Google Scholar
11	Rao Q, Cheng L, Xia QY, et al: Cathepsin K expression in a wide spectrum of perivascular epithelioid cell neoplasms (PEComas): a clinicopathological study emphasizing extrarenal PEComas. Histopathology. 62:642–650. 2013. View Article : Google Scholar : PubMed/NCBI
12	Jevnikar Z, Rojnik M, Jamnik P, Doljak B, Fonovic UP and Kos J: Cathepsin H mediates the processing of talin and regulates migration of prostate cancer cells. J Biol Chem. 288:2201–2209. 2013. View Article : Google Scholar : PubMed/NCBI
13	Nakashima T, Yasumatsu R, Masuda M, Clayman GL and Komune S: Prognostic value of cathepsin L and its inhibitor headpin in oral squamous cell carcinoma. J Laryngol Otol. 126:1134–1137. 2012. View Article : Google Scholar : PubMed/NCBI
14	Bar-Sela G, Kaplan-Cohen V, Ilan N, Vlodavsky I and Ben-Izhak O: Heparanase expression in nasopharyngeal carcinoma inversely correlates with patient survival. Histopathology. 49:188–193. 2006. View Article : Google Scholar : PubMed/NCBI
15	Zhang W, Hu XX, Yang XZ, et al: Combined detection of serum matrix metalloproteinase 9, acetyl heparinase and cathepsin L in diagnosis of ovarian cancer. Chin J Cancer Res. 24:67–71. 2012. View Article : Google Scholar : PubMed/NCBI
16	Sivaparvathi M, Yamamoto M, Nicolson GL, et al: Expression and immunohistochemical localization of cathepsin L during the progression of human gliomas. Clin Exp Metastasis. 14:27–34. 1996. View Article : Google Scholar : PubMed/NCBI
17	Tumminello FM, Leto G, Pizzolanti G, et al: Cathepsin D, B and L circulating levels as prognostic markers of malignant progression. Anticancer Res. 16:2315–2319. 1996.PubMed/NCBI
18	Friedrich B, Jung K, Lein M, et al: Cathepsins B, H, L and cysteine protease inhibitors in malignant prostate cell lines, primary cultured prostatic cells and prostatic tissue. Eur J Cancer. 35:138–144. 1999. View Article : Google Scholar : PubMed/NCBI
19	Svatek RS, Karam J, Karakiewicz PI, et al: Role of urinary cathepsin B and L in the detection of bladder urothelial cell carcinoma. J Urol. 179:478–484. 2008. View Article : Google Scholar : PubMed/NCBI
20	Sheahan K, Shuja S and Murnane MJ: Cysteine protease activities and tumor development in human colorectal carcinoma. Cancer Res. 49:3809–3814. 1989.PubMed/NCBI
21	Watanabe M, Higashi T, Hashimoto M, et al: Elevation of tissue cathepsin B and L activities in gastric cancer. Hepatogastroenterology. 34:120–122. 1987.PubMed/NCBI
22	Gabrijelcic D, Svetic B, Spaić D, et al: Cathepsins B, H and L in human breast carcinoma. Eur J Clin Chem Clin Biochem. 30:69–74. 1992.PubMed/NCBI
23	Niedergethmann M, Wostbrock B, Sturm JW, Willeke F, Post S and Hildenbrand R: Prognostic impact of cysteine proteases cathepsin B and cathepsin L in pancreatic adenocarcinoma. Pancreas. 29:204–211. 2004. View Article : Google Scholar : PubMed/NCBI
24	Casson AG, Wilson SM, McCart JA, et al: ras mutation and expression of the ras-regulated genes osteopontin and cathepsin L in human esophageal cancer. Int J Cancer. 72:739–745. 1997. View Article : Google Scholar : PubMed/NCBI
25	Samaiya M, Bakhshi S, Shukla AA, Kumar L and Chauhan SS: Epigenetic regulation of cathepsin L expression in chronic myeloid leukaemia. J Cell Mol Med. 15:2189–2199. 2011. View Article : Google Scholar : PubMed/NCBI
26	De Luca A, Maiello MR, D’Alessio A, Pergameno M and Normanno N: The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets. 16(Suppl 2): S17–S27. 2012.PubMed/NCBI
27	Zhang W, Ling D, Tan J, Zhang J and Li L: Expression of urokinase plasminogen activator and plasminogen activator inhibitor type-1 in ovarian cancer and its clinical significance. Oncol Rep. 29:637–645. 2013.PubMed/NCBI
28	Goldman S and Shalev E: MMPS and TIMPS in ovarian physiology and pathophysiology. Front Biosci. 9:2474–2483. 2004. View Article : Google Scholar : PubMed/NCBI