Expression levels of seprase/FAPα and DPPIV/CD26 in epithelial ovarian carcinoma

Zhang,Mengzhen; Xu,Liwei; Wang,Xiaoling; Sun,Beibei; Ding,Juan

doi:10.3892/ol.2015.3151

Expression levels of seprase/FAPα and DPPIV/CD26 in epithelial ovarian carcinoma

Authors:
- Mengzhen Zhang
- Liwei Xu
- Xiaoling Wang
- Beibei Sun
- Juan Ding
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Affiliations: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: April 27, 2015 https://doi.org/10.3892/ol.2015.3151
Pages: 34-42
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dipeptidyl peptidase IV (DPPIV; also known as cluster of differentiation 26) and the surface‑expressed protease, seprase [also known as fibroblast activation protein alpha (FAPα)], are able to degrade the extracellular matrix; therefore, they are involved in malignant cell invasion and metastasis. However, the prognostic implications of their overexpression in carcinomas remain controversial. The aim of the present study was to investigate the expression and potential prognostic effects of DPPIV and seprase in cases of ovarian carcinoma. Immunohistochemical analysis (IHC) was performed to assess the protein expression of DPPIV and seprase/FAPα in 199 patients (malignant epithelial ovarian cancer, 128; borderline ovarian tumors, 41; and benign ovarian tumors, 30). In addition, in situ hybridization was used to detect the mRNA expression levels of DPPIV and seprase in 86 malignant epithelial ovarian cancer samples. IHC revealed positive staining for seprase and DPPIV proteins in 110/128 (85.94%) and 106/128 (82.81%) patients with ovarian cancer, respectively. Seprase and DPPIV protein expression was associated with lymph node metastasis and the International Federation of Gynecology and Obstetrics stage. By contrast, no significant correlation was detected between the proteins and the patient age or histological grade and type of tumor. Immunostaining was stronger in the cancerous tissues compared with the borderline and benign tissues. Increased levels of seprase, but not DPPIV, were significantly associated with a shorter disease‑free survival (P=0.033). Further analysis revealed that 96.5 (83/86) and 97.67% (84/86) of the malignant epithelial ovarian cancer samples stained positively for seprase and DPPIV mRNA, respectively. Therefore, DPPIV and seprase may be involved in the development of ovarian cancer, and that they are potential predictive markers of epithelial ovarian carcinoma.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Aletti GD, Gallenberg MM, Cliby WA, Jatoi A and Hartmann LC: Current management strategies for ovarian cancer. Mayo Clin Proc. 82:751–770. 2007. View Article : Google Scholar : PubMed/NCBI
3	Morrison J: Advances in the understanding and treatment of ovarian cancer. J Br Menopause Soc. 11:66–71. 2005. View Article : Google Scholar : PubMed/NCBI
4	Bakrin N, Bereder JM, Decullier E, Classe JM, et al: FROGHI (French Oncologic and Gynecologic HIPEC) Group: Peritoneal carcinomatosis treated with cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for advanced ovarian carcinoma: a French multicentre retrospective cohort study of 566 patients. Eur J Surg Oncol. 39:1435–1443. 2013. View Article : Google Scholar : PubMed/NCBI
5	Coleman RL, Monk BJ, Sood AK and Herzog TJ: Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol. 10:211–224. 2013. View Article : Google Scholar : PubMed/NCBI
6	Werb Z: ECM and cell surface proteolysis: regulating cellular ecology. Cell. 91:439–442. 1997. View Article : Google Scholar : PubMed/NCBI
7	Talvensaari-Mattila A, Santala M, Soini Y and Turpeenniemi-Hujanen T: Prognostic value of matrix metalloproteinase-2 (MMP-2) expression in endometrial endometrioid adenocarcinoma. Anticancer Res. 25:4101–4105. 2005.PubMed/NCBI
8	Rowe RG and Weiss SJ: Navigating ECM barriers at the invasive front: the cancer cell-stroma interface. Annu Rev Cell Dev Biol. 25:567–595. 2009. View Article : Google Scholar : PubMed/NCBI
9	Deakin NE and Chaplain MA: Mathematical modeling of cancer invasion: the role of membrane-bound matrix metalloproteinases. Front Oncol. 3:702013.PubMed/NCBI
10	Chen WT, Kelly T and Ghersi G: DPPIV, seprase and related serine peptidases in multiple cellular functions. Curr Top Dev Biol. 54:207–232. 2003.PubMed/NCBI
11	Goscinski MA, Suo ZH, Nesland JM, Flørenes VA and Giercksky KE: Dipeptidyl peptidase IV expression in cancer and stromal cells of human esophageal squamous cell carcinomas, adenocarcinomas and squamous cell carcinoma cell lines. APMIS. 116:823–831. 2008. View Article : Google Scholar : PubMed/NCBI
12	Mentlein R, Hattermann K, Hemion C, Jungbluth AA and Held-Feindt J: Expression and role of the cell surface protease seprase/fibroblast activation protein-α (FAP-α) in astroglial tumors. Biol Chem. 392:199–207. 2011.PubMed/NCBI
13	Benedet JL, Bender H, Jones H III, Ngan HY and Pecorelli S: FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 70:209–262. 2000. View Article : Google Scholar : PubMed/NCBI
14	Wu Q, Suo Z, Risbegr B, Karlsson MG, Villman K and Nesland JM: Expression of EPhb2 And Ephb4 in Berast Caerinoma. Phatol oneol Res. 10:26–33. 2004.
15	Lawrie LC, Curran S, MeLeod HL, Fothergill JE and Murray GI: Applieation of laser capture microdissection and porteomics in colon cancer. Mol Pathol. 54:253–258. 2001. View Article : Google Scholar : PubMed/NCBI
16	Monsky WL, Lin CY, Aoyama A, Kelly T, Akiyama SK, Mueller SC and Chen WT: A potential marker protease of invasiveness, seprase, is localized on invadopodia of human malignant melanoma cells. Cancer Res. 54:5702–5710. 1994.PubMed/NCBI
17	Chen WT and Kelly T: Seprase complexes in cellular invasiveness. Cancer Metastasis Rev. 22:259–269. 2003. View Article : Google Scholar : PubMed/NCBI
18	Kotacková L, Baláziová E and Sedo A: Expression pattern of dipeptidyl peptidase IV activity and/or structure homologues in cancer. Folia Biol (Praha). 55:77–84. 2009.PubMed/NCBI
19	Pro B and Dang NH: CD26/dipeptidyl peptidase IV and its role in cancer. Histol Histopathol. 19:1345–1351. 2004.PubMed/NCBI
20	Mueller SC, Ghersi G, Akiyama SK, Sang QX, Howard L, Pineiro-Sanchez M, et al: A novel protease-docking function of integrin at invadopodia. J Biol Chem. 274:24947–24952. 1999. View Article : Google Scholar : PubMed/NCBI
21	O'Brien P and O'Connor BF: Seprase: an overview of an important matrix serine protease. Biochim Biophys Acta. 1784:1130–1145. 2008. View Article : Google Scholar : PubMed/NCBI
22	Kelly T, Kechelava S, Rozypal TL, West KW and Korourian S: Seprase, a membrane-bound protease, is overexpressed by invasive ductal carcinoma cells of human breast cancers. Mod Pathol. 11:855–863. 1998.PubMed/NCBI
23	Jin X, Iwasa S, Okada K, Mitsumata M and Ooi A: Expression patterns of seprase, a membrane serine protease, in cervical carcinoma and cervical intraepithelial neoplasm. Anticancer Res. 23:3195–3198. 2003.PubMed/NCBI
24	Okada K, Chen WT, Iwasa S, Jin X, Yamane T, Ooi A and Mitsumata M: Seprase, a membrane-type serine protease, has different expression patterns in intestinal- and diffuse-type gastric cancer. Oncology. 65:363–370. 2003. View Article : Google Scholar : PubMed/NCBI
25	Wikberg ML, Edin S, Lundberg IV, Van Guelpen B, Dahlin AM, Rutegård J, et al: High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis. Tumour Biol. 34:1013–1020. 2013. View Article : Google Scholar : PubMed/NCBI
26	Huang Y, Wang S and Kelly T: Seprase promotes rapid tumor growth and increased microvessel density in a mouse model of human breast cancer. Cancer Res. 64:2712–2716. 2004. View Article : Google Scholar : PubMed/NCBI
27	Ariga N, Sato E, Ohuchi N, Nagura H and Ohtani H: Stromal expression of fibroblast activation protein/seprase, a cell membrane serine proteinase and gelatinase, is associated with longer survival in patients with invasive ductal carcinoma of breast. Int J Cancer. 95:67–72. 2001. View Article : Google Scholar : PubMed/NCBI
28	Wilson MJ, Ruhland AR, Quast BJ, Reddy PK, Ewing SL and Sinha AA: Dipeptidylpeptidase IV activities are elevated in prostate cancers and adjacent benign hyperplastic glands. J Androl. 21:220–226. 2000.PubMed/NCBI
29	Khin EE, Kikkawa F, Ino K, Kajiyama H, Suzuki T, Shibata K, et al: Dipeptidyl peptidase IV expression in endometrial endometrioid adenocarcinoma and its inverse correlation with tumor grade. Am J Obstet Gynecol. 188:670–676. 2003. View Article : Google Scholar : PubMed/NCBI
30	Mizokami Y, Kajiyama H, Shibata K, Ino K, Kikkawa F and Mizutani S: Stromal cell-derived factor-1alpha-induced cell proliferation and its possible regulation by CD26/dipeptidyl peptidase IV in endometrial adenocarcinoma. Int J Cancer. 110:652–659. 2004. View Article : Google Scholar : PubMed/NCBI
31	Abe M, Havre PA, Urasaki Y, Ohnuma K, Morimoto C, Dang LH and Dang NH: Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines. BMC Cancer. 11:512011. View Article : Google Scholar : PubMed/NCBI
32	Miyake Y, Aratake Y, Sakaguchi T, Kiyoya K, Kuribayashi T, Marutsuka K and Ohno E: Examination of CD26/DPPIV, p53 and PTEN expression in thyroid follicular adenoma. Diagn Cytopathol. 40:1047–1053. 2012. View Article : Google Scholar : PubMed/NCBI
33	Kajiyama H, Kikkawa F, Suzuki T, Shibata K, Ino K and Mizutani S: Prolonged survival and decreased invasive activity attributable to dipeptidyl peptidase IV overexpression in ovarian carcinoma. Cancer Res. 62:2753–2757. 2002.PubMed/NCBI
34	Kennedy A, Dong H, Chen D and Chen WT: Elevation of seprase expression and promotion of an invasive phenotype by collagenous matrices in ovarian tumor cells. Int J Cancer. 124:27–35. 2009. View Article : Google Scholar : PubMed/NCBI
35	Lai D, Ma L and Wang F: Fibroblast activation protein regulates tumor-associated fibroblasts and epithelial ovarian cancer cells. Int J Oncol. 41:541–550. 2012.PubMed/NCBI
36	Yang L, Ma L and Lai D: Over-expression of fibroblast activation protein alpha increases tumor growth in xenografts of ovarian cancer cells. Acta Biochim Biophys Sin (Shanghai). 45:928–937. 2013. View Article : Google Scholar : PubMed/NCBI