nach oben

Erschienen in:

01.01.2010 | Research Paper

Protease inhibitor SERPINA1 expression in epithelial ovarian cancer

verfasst von: Karine Normandin, Benjamin Péant, Cécile Le Page, Manon de Ladurantaye, Véronique Ouellet, Patricia N. Tonin, Diane M. Provencher, Anne-Marie Mes-Masson

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 1/2010

Einloggen, um Zugang zu erhalten

Abstract

Epithelial ovarian cancer is the most lethal gynecologic cancer with a 5 years survival rate of 30–40% in patients diagnosed with high-grade invasive disease (TOV). This is in stark contrast to the 95% 5 years survival rate in ovarian cancer patients diagnosed with low malignant potential (LMP) disease. The progression from localized tumor to invasive metastasis involves matrix proteolysis. Protease inhibitors are thought to play a key role by limiting this process. Using the Affymetrix HG-U133A GeneChip array, we have studied all serine protease inhibitors and found several serpin family members that are differentially expressed between LMP and TOV serous tumors. SERPINA1 was selected for further study due to its high expression in the majority of LMP tumors and its low expression in TOV tumors; observations that were also validated by quantitative-PCR (Q-PCR). To study the effects of its over expression on different tumorigenic parameters, SERPINA1 was cloned in the pcDNA3.1+ plasmid which was subsequently used to derive stable clones from two invasive ovarian cancer cell lines, TOV-112D and TOV-1946. We found no effect of SERPINA1 over expression on tumor growth in SCID mice although cell migration and invasion were affected in in vitro assays. There was also no association between patient survival and SERPINA1 immunostaining, however, SERPINA1 localization was different in LMP (nuclear) and TOV (cytoplasmic) tumors. SERPINA1 remains an interesting candidate since protein homeostasis, regulated by proteases and their inhibitors, should be studied holistically in order to assess their full impact in tumor progression.

Nur mit Berechtigung zugänglich

Permuth-Wey J, Sellers TA (2009) Epidemiology of ovarian cancer. Methods Mol Biol 472:413–437CrossRefPubMed

Colombo N, Van Gorp T, Parma G et al (2006) Ovarian cancer. Crit Rev Oncol Hematol 60:159–179CrossRefPubMed

Bell DA (2005) Origins and molecular pathology of ovarian cancer. Mod Pathol 18(Suppl 2):S19–S32CrossRefPubMed

Crum CP, Drapkin R, Kindelberger D et al (2007) Lessons from BRCA: the tubal fimbria emerges as an origin for pelvic serous cancer. Clin Med Res 5:35–44CrossRefPubMed

Crum CP, Drapkin R, Miron A et al (2007) The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 19:3–9CrossRefPubMed

Benedet JL (2006) Staging classifications and clinical practice guidelines for gynaecologic cancers. In: Publications of the international federation of gynecology and obstetrics. Available via http://www.figo.org/publications

Bell DA, Longacre TA, Prat J et al (2004) Serous borderline (low malignant potential, atypical proliferative) ovarian tumors: workshop perspectives. Hum Pathol 35:934–948CrossRefPubMed

Singer G, Oldt R III, Cohen Y et al (2003) Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma. J Natl Cancer Inst 95:484–486PubMedCrossRef

Singer G, Stohr R, Cope L et al (2005) Patterns of p53 mutations separate ovarian serous borderline tumors and low- and high-grade carcinomas and provide support for a new model of ovarian carcinogenesis: a mutational analysis with immunohistochemical correlation. Am J Surg Pathol 29:218–224CrossRefPubMed

10.

Bonome T, Lee JY, Park DC et al (2005) Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary. Cancer Res 65:10602–10612CrossRefPubMed

11.

Chen VW, Ruiz B, Killeen JL et al (2003) Pathology and classification of ovarian tumors. Cancer 97:2631–2642CrossRefPubMed

12.

Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572CrossRefPubMed

13.

Friedl P, Wolf K (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362–374CrossRefPubMed

14.

Aznavoorian S, Murphy AN, Stetler-Stevenson WG et al (1993) Molecular aspects of tumor cell invasion and metastasis. Cancer 71:1368–1383CrossRefPubMed

15.

Duffy MJ (1992) The role of proteolytic enzymes in cancer invasion and metastasis. Clin Exp Metastasis 10:145–155CrossRefPubMed

16.

Duffy MJ (1996) Proteases as prognostic markers in cancer. Clin Cancer Res 2:613–618PubMed

17.

Schmitt M (1992) Tumor associated proteases. Fibrinolysis 6:3–26CrossRef

18.

Gettins PG (2002) Serpin structure, mechanism, and function. Chem Rev 102:4751–4804CrossRefPubMed

19.

van Gent D, Sharp P, Morgan K et al (2003) Serpins: structure, function and molecular evolution. Int J Biochem Cell Biol 35:1536–1547CrossRefPubMed

20.

de Koning PJ, Bovenschen N, Leusink FK et al (2009) Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome. Int J Cancer 125:1542–1550CrossRefPubMed

21.

Croucher DR, Saunders DN, Lobov S et al (2008) Revisiting the biological roles of PAI2 (SERPINB2) in cancer. Nat Rev Cancer 8:535–545CrossRefPubMed

22.

Bailey CM, Khalkhali-Ellis Z, Seftor EA et al (2006) Biological functions of maspin. J Cell Physiol 209:617–624CrossRefPubMed

23.

Zou Z, Anisowicz A, Hendrix MJ et al (1994) Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science 263:526–529CrossRefPubMed

24.

Sieben NL, Oosting J, Flanagan AM et al (2005) Differential gene expression in ovarian tumors reveals Dusp 4 and Serpina 5 as key regulators for benign behavior of serous borderline tumors. J Clin Oncol 23:7257–7264CrossRefPubMed

25.

Tamura K, Furihata M, Tsunoda T et al (2007) Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles. Cancer Res 67:5117–5125CrossRefPubMed

26.

Warrenfeltz S, Pavlik S, Datta S et al (2004) Gene expression profiling of epithelial ovarian tumours correlated with malignant potential. Mol Cancer 3:27CrossRefPubMed

27.

Carlson JA, Rogers BB, Sifers RN et al (1988) Multiple tissues express alpha 1-antitrypsin in transgenic mice and man. J Clin Invest 82:26–36CrossRefPubMed

28.

Carrell RW (1986) alpha 1-Antitrypsin: molecular pathology, leukocytes, and tissue damage. J Clin Invest 78:1427–1431CrossRefPubMed

29.

Kalsheker N, Morley S, Morgan K (2002) Gene regulation of the serine proteinase inhibitors alpha1-antitrypsin and alpha1-antichymotrypsin. Biochem Soc Trans 30:93–98CrossRefPubMed

30.

Kohnlein T, Welte T (2008) Alpha-1 antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment. Am J Med 121:3–9CrossRefPubMed

31.

Law RH, Zhang Q, McGowan S et al (2006) An overview of the serpin superfamily. Genome Biol 7:216CrossRefPubMed

32.

Lisowska-Myjak B (2005) AAT as a diagnostic tool. Clin Chim Acta 352:1–13CrossRefPubMed

33.

Silverman GA, Bird PI, Carrell RW et al (2001) The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J Biol Chem 276:33293–33296CrossRefPubMed

34.

Travis J, Salvesen GS (1983) Human plasma proteinase inhibitors. Annu Rev Biochem 52:655–709CrossRefPubMed

35.

Ouellet V, Zietarska M, Portelance L et al (2008) Characterization of three new serous epithelial ovarian cancer cell lines. BMC Cancer 8:152CrossRefPubMed

36.

Provencher DM, Lounis H, Champoux L et al (2000) Characterization of four novel epithelial ovarian cancer cell lines. In Vitro Cell Dev Biol Anim 36:357–361CrossRefPubMed

37.

Ouellet V, Provencher DM, Maugard CM et al (2005) Discrimination between serous low malignant potential and invasive epithelial ovarian tumors using molecular profiling. Oncogene 24:4672–4687CrossRefPubMed

38.

Puiffe ML, Le Page C, Filali-Mouhim A et al (2007) Characterization of ovarian cancer ascites on cell invasion, proliferation, spheroid formation, and gene expression in an in vitro model of epithelial ovarian cancer. Neoplasia 9:820–829CrossRefPubMed

39.

Novak JP, Sladek R, Hudson TJ (2002) Characterization of variability in large-scale gene expression data: implications for study design. Genomics 79:104–113CrossRefPubMed

40.

Golub TR, Slonim DK, Tamayo P et al (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286:531–537CrossRefPubMed

41.

Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A 98:5116–5121CrossRefPubMed

42.

Peant B, Diallo JS, Dufour F et al (2009) Over-expression of IkappaB-kinase-epsilon (IKKepsilon/IKKi) induces secretion of inflammatory cytokines in prostate cancer cell lines. Prostate 69:706–718CrossRefPubMed

43.

Wolf K, Wu YI, Liu Y et al (2007) Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol 9:893–904CrossRefPubMed

44.

Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70CrossRefPubMed

45.

Ludwig T (2005) Local proteolytic activity in tumor cell invasion and metastasis. Bioessays 27:1181–1191CrossRefPubMed

46.

Sato T, Takahashi S, Mizumoto T et al (2006) Neutrophil elastase and cancer. Surg Oncol 15:217–222CrossRefPubMed

47.

Kobel M, Kalloger SE, Boyd N et al (2008) Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med 5:e232CrossRefPubMed

48.

Li W, Savinov AY, Rozanov DV et al (2004) Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies and targets alpha1-antitrypsin serpin. Cancer Res 64:8657–8665CrossRefPubMed

49.

O’Neill CJ, McBride HA, Connolly LE et al (2007) High-grade ovarian serous carcinoma exhibits significantly higher p16 expression than low-grade serous carcinoma and serous borderline tumour. Histopathology 50:773–779CrossRefPubMed

50.

Ouellet V, Ling TH, Normandin K et al (2008) Immunohistochemical profiling of benign, low malignant potential and low grade serous epithelial ovarian tumors. BMC Cancer 8:346CrossRefPubMed

51.

Schmeler KM, Gershenson DM (2008) Low-grade serous ovarian cancer: a unique disease. Curr Oncol Rep 10:519–523CrossRefPubMed

52.

Wolf K, Mazo I, Leung H et al (2003) Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 160:267–277CrossRefPubMed

53.

Wong SY, Hynes RO (2006) Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide? Cell Cycle 5:812–817PubMed

54.

Taetle R, Aickin M, Yang JM et al (1999) Chromosome abnormalities in ovarian adenocarcinoma: I. Nonrandom chromosome abnormalities from 244 cases. Genes Chromosomes Cancer 25:290–300CrossRefPubMed

55.

Bagdasarian A, Wheeler J, Stewart GJ et al (1981) Isolation of alpha 1-protease inhibitor from human normal and malignant ovarian tissue. J Clin Invest 67:281–291CrossRefPubMed

56.

Ny T, Wahlberg P, Brandstrom IJ (2002) Matrix remodeling in the ovary: regulation and functional role of the plasminogen activator and matrix metalloproteinase systems. Mol Cell Endocrinol 187:29–38CrossRefPubMed

57.

Allgayer H, Babic R, Grutzner KU et al (1998) Tumor-associated proteases and inhibitors in gastric cancer: analysis of prognostic impact and individual risk protease patterns. Clin Exp Metastasis 16:62–73CrossRefPubMed

58.

Karashima S, Kataoka H, Itoh H et al (1990) Prognostic significance of alpha-1-antitrypsin in early stage of colorectal carcinomas. Int J Cancer 45:244–250CrossRefPubMed

59.

Higashiyama M, Doi O, Kodama K et al (1992) An evaluation of the prognostic significance of alpha-1-antitrypsin expression in adenocarcinomas of the lung: an immunohistochemical analysis. Br J Cancer 65:300–302PubMed

60.

Kloth JN, Gorter A, Fleuren GJ et al (2008) Elevated expression of SerpinA1 and SerpinA3 in HLA-positive cervical carcinoma. J Pathol 215:222–230CrossRefPubMed

61.

Sood AK, Fletcher MS, Gruman LM et al (2002) The paradoxical expression of maspin in ovarian carcinoma. Clin Cancer Res 8:2924–2932PubMed

62.

Keppler D, Markert M, Carnal B et al (1996) Human colon carcinoma cells synthesize and secrete alpha 1-proteinase inhibitor. Biol Chem Hoppe Seyler 377:301–311PubMed

63.

Yavelow J, Tuccillo A, Kadner SS et al (1997) Alpha 1-antitrypsin blocks the release of transforming growth factor-alpha from MCF-7 human breast cancer cells. J Clin Endocrinol Metab 82:745–752CrossRefPubMed

64.

Lah TT, Duran Alonso MB, Van Noorden CJ (2006) Antiprotease therapy in cancer: hot or not? Expert Opin Biol Ther 6:257–279CrossRefPubMed

Titel: Protease inhibitor SERPINA1 expression in epithelial ovarian cancer
verfasst von: Karine Normandin
Benjamin Péant
Cécile Le Page
Manon de Ladurantaye
Véronique Ouellet
Patricia N. Tonin
Diane M. Provencher
Anne-Marie Mes-Masson
Publikationsdatum: 01.01.2010
Verlag: Springer Netherlands
Erschienen in: Clinical & Experimental Metastasis / Ausgabe 1/2010
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-009-9303-6

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Protease inhibitor SERPINA1 expression in epithelial ovarian cancer

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2010

Leptomeningeal metastases from prostate cancer: an emerging clinical conundrum

Inhibition of metastasis in a murine 4T1 breast cancer model by liposomes preventing tumor cell-platelet interactions

Protease-activated receptor-1 (PAR-1) promotes the motility of human melanomas and is associated to their metastatic phenotype

Modeling liver metastasis using a tumor cell line derived from an enhanced green fluorescent protein transgenic mouse

Candida albicans enhances experimental hepatic melanoma metastasis

Gene expression profiling of primary and metastatic colon cancers identifies a reduced proliferative rate in metastatic tumors

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie