Formyl peptide receptor 2 expression predicts poor prognosis and promotes invasion and metastasis in epithelial ovarian cancer

Xie,Xiaohui; Yang,Mengyuan; Ding,Yiling; Yu,Ling; Chen,Jianlin

doi:10.3892/or.2017.6034

Formyl peptide receptor 2 expression predicts poor prognosis and promotes invasion and metastasis in epithelial ovarian cancer

Authors:
- Xiaohui Xie
- Mengyuan Yang
- Yiling Ding
- Ling Yu
- Jianlin Chen
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
Published online on: October 13, 2017 https://doi.org/10.3892/or.2017.6034
Pages: 3297-3308
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Formyl peptide receptor 2 (FPR2) has been identified as a member of the G protein-coupled chemoattractant receptor (GPCR) family and has been implicated as playing a role in both inflammation and cancer development. Epithelial ovarian cancer (EOC) has been suggested to be correlated with both infectious and non-infectious inflammation. To date, the role of FPR2 in EOC remains poorly understood and controversial. In the present study, we aimed to investigate the potential of FPR2 in regulating EOC. We performed immunohistochemistry and RT-qPCR to analyzed expression of FPR2 in EOC tissues and the correlation between FPR2 and EOC clinicopathological characteristics as well as prognosis were also analyzed. To test the role of FPR2 in EOC cell migration, we established FPR2-knockdown SKOV3 cells and performed wound-healing, Transwell and angiogenesis assays to detect the metastatic potential of these EOC cells. Our studies found that FPR2 was overexpressed in EOC tissues and was positively correlated with EOC clinicopathological characteristics including the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and ovarian cancer type. Survival analyses suggested that FPR2 overexpression indicated the poorer prognosis of EOC patients and FPR2 may act as an independent risk factor for EOC prognosis. FPR2 knockdown decreased the migration potential of the ovarian cancer cells. Moreover, serum amyloid A (SAA) may stimulate the migration of SKOV3 cells through FPR2. The present study suggested that FPR2 promoted the invasion and metastasis of EOC and it could be a prognostic marker for EOC.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Chen W: Cancer statistics: Updated cancer burden in China. Chin J Cancer Res. 27:12015. View Article : Google Scholar : PubMed/NCBI
3	Herzog TJ and Pothuri B: Ovarian cancer: A focus on management of recurrent disease. Nat Clin Pract Oncol. 3:604–611. 2006. View Article : Google Scholar : PubMed/NCBI
4	Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM and Silva EG: Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol. 28:496–504. 2004. View Article : Google Scholar : PubMed/NCBI
5	Kurman RJ and Shih IeM: The origin and pathogenesis of epithelial ovarian cancer: A proposed unifying theory. Am J Surg Pathol. 34:433–443. 2010. View Article : Google Scholar : PubMed/NCBI
6	Hunn J and Rodriguez GC: Ovarian cancer: Etiology, risk factors, and epidemiology. Clin Obstet Gynecol. 55:3–23. 2012. View Article : Google Scholar : PubMed/NCBI
7	Lin HW, Tu YY, Lin SY, Su WJ, Lin WL, Lin WZ, Wu SC and Lai YL: Risk of ovarian cancer in women with pelvic inflammatory disease: A population-based study. Lancet Oncol. 12:900–904. 2011. View Article : Google Scholar : PubMed/NCBI
8	Risch HA and Howe GR: Pelvic inflammatory disease and the risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev. 4:447–451. 1995.PubMed/NCBI
9	Seidman JD, Sherman ME, Bell KA, Katabuchi H, O'Leary TJ and Kurman RJ: Salpingitis, salpingoliths, and serous tumors of the ovaries: Is there a connection? Int J Gynecol Pathol. 21:101–107. 2002. View Article : Google Scholar : PubMed/NCBI
10	Ye RD, Boulay F, Wang JM, Dahlgren C, Gerard C, Parmentier M, Serhan CN and Murphy PM: International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol Rev. 61:119–161. 2009. View Article : Google Scholar : PubMed/NCBI
11	Becker EL, Forouhar FA, Grunnet ML, Boulay F, Tardif M, Bormann BJ, Sodja D, Ye RD, Woska JR Jr and Murphy PM: Broad immunocytochemical localization of the formylpeptide receptor in human organs, tissues, and cells. Cell Tissue Res. 292:129–135. 1998. View Article : Google Scholar : PubMed/NCBI
12	Migeotte I, Communi D and Parmentier M: Formyl peptide receptors: A promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev. 17:501–519. 2006. View Article : Google Scholar : PubMed/NCBI
13	Li Y and Ye D: Molecular biology for formyl peptide receptors in human diseases. J Mol Med. 91:781–789. 2013. View Article : Google Scholar : PubMed/NCBI
14	Coffelt SB, Tomchuck SL, Zwezdaryk KJ, Danka ES and Scandurro AB: Leucine leucine-37 uses formyl peptide receptor-like 1 to activate signal transduction pathways, stimulate oncogenic gene expression, and enhance the invasiveness of ovarian cancer cells. Mol Cancer Res. 7:907–915. 2009. View Article : Google Scholar : PubMed/NCBI
15	Urieli-Shoval S, Finci-Yeheskel Z, Dishon S, Galinsky D, Linke RP, Ariel I, Levin M, Ben-Shachar I and Prus D: Expression of serum amyloid a in human ovarian epithelial tumors: Implication for a role in ovarian tumorigenesis. J Histochem Cytochem. 58:1015–1023. 2010. View Article : Google Scholar : PubMed/NCBI
16	Liang TS, Wang JM, Murphy PM and Gao JL: Serum amyloid A is a chemotactic agonist at FPR2, a low-affinity N-formylpeptide receptor on mouse neutrophils. Biochem Biophys Res Commun. 270:331–335. 2000. View Article : Google Scholar : PubMed/NCBI
17	Ren SW, Qi X, Jia CK and Wang YQ: Serum amyloid A and pairing formyl peptide receptor 2 are expressed in corneas and involved in inflammation-mediated neovascularization. Int J Ophthalmol. 7:187–193. 2014.PubMed/NCBI
18	Yang M, Liu F and Higuchi K, Sawashita J, Fu X, Zhang L, Zhang L, Fu L, Tong Z and Higuchi K: Serum amyloid A expression in the breast cancer tissue is associated with poor prognosis. Oncotarget. 7:35843–35852. 2016.PubMed/NCBI
19	Romero I and Bast RC Jr: Minireview: Human ovarian cancer: Biology, current management, and paths to personalizing therapy. Endocrinology. 153:1593–1602. 2012. View Article : Google Scholar : PubMed/NCBI
20	Oldekamp S, Pscheidl S, Kress E, Soehnlein O, Jansen S, Pufe T, Wang JM, Tauber SC and Brandenburg LO: Lack of formyl peptide receptor 1 and 2 leads to more severe inflammation and higher mortality in mice with of pneumococcal meningitis. Immunology. 143:447–461. 2014. View Article : Google Scholar : PubMed/NCBI
21	Xiang Y, Yao X, Chen K, Wang X, Zhou J, Gong W, Yoshimura T, Huang J, Wang R, Wu Y, et al: The G-protein coupled chemoattractant receptor FPR2 promotes malignant phenotype of human colon cancer cells. Am J Cancer Res. 6:2599–2610. 2016.PubMed/NCBI
22	Khau T, Langenbach SY, Schuliga M, Harris T, Johnstone CN, Anderson RL and Stewart AG: Annexin-1 signals mitogen-stimulated breast tumor cell proliferation by activation of the formyl peptide receptors (FPRs) 1 and 2. FASEB J. 25:483–496. 2011. View Article : Google Scholar : PubMed/NCBI
23	Wang J, Sharma A, Ghamande SA, Bush S, Ferris D, Zhi W, He M, Wang M, Wang X, Miller E, et al: Serum protein profile at remission can accurately assess therapeutic outcomes and survival for serous ovarian cancer. PLoS One. 8:e783932013. View Article : Google Scholar : PubMed/NCBI
24	Sodin-Semrl S, Spagnolo A, Mikus R, Barbaro B, Varga J and Fiore S: Opposing regulation of interleukin-8 and NF-kappaB responses by lipoxin A4 and serum amyloid A via the common lipoxin A receptor. Int J Immunopathol Pharmacol. 17:145–156. 2004. View Article : Google Scholar : PubMed/NCBI
25	Badolato R, Wang JM, Murphy WJ, Lloyd AR, Michiel DF, Bausserman LL, Kelvin DJ and Oppenheim JJ: Serum amyloid A is a chemoattractant: Induction of migration, adhesion, and tissue infiltration of monocytes and polymorphonuclear leukocytes. J Exp Med. 180:203–209. 1994. View Article : Google Scholar : PubMed/NCBI
26	Yazawa H, Yu ZX, Takeda, Le Y, Gong W, Ferrans VJ, Oppenheim JJ, Li CC and Wang JM: β amyloid peptide (Aβ42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. FASEB J. 15:2454–2462. 2001. View Article : Google Scholar : PubMed/NCBI
27	Duvernay MT, Filipeanu CM and Wu G: The regulatory mechanisms of export trafficking of G protein-coupled receptors. Cell Signal. 17:1457–1465. 2005. View Article : Google Scholar : PubMed/NCBI
28	Byrne AT, Ross L, Holash J, Nakanishi M, Hu L, Hofmann JI, Yancopoulos GD and Jaffe RB: Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin Cancer Res. 9:5721–5728. 2003.PubMed/NCBI
29	Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, et al: ICON7 Investigators: A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 365:2484–2496. 2011. View Article : Google Scholar : PubMed/NCBI
30	Lu Q, Quan W, Wu J, Zhang X, Ma W, Pang L and Li D: Effect of antibacterial peptide hCAP18/LL-37 on ovarian cancer microenvironment and the regulatory mechanism of its expression. Zhonghua Zhong Liu Za Zhi. 37:725–730. 2015.(In Chinese). PubMed/NCBI
31	Pesic M and Greten FR: Inflammation and cancer: Tissue regeneration gone awry. Curr Opin Cell Biol. 43:55–61. 2016. View Article : Google Scholar : PubMed/NCBI
32	Karin M and Clevers H: Reparative inflammation takes charge of tissue regeneration. Nature. 529:307–315. 2016. View Article : Google Scholar : PubMed/NCBI
33	Kim BH, Yi EH and Ye SK: Signal transducer and activator of transcription 3 as a therapeutic target for cancer and the tumor microenvironment. Arch Pharm Res. 39:1085–1099. 2016. View Article : Google Scholar : PubMed/NCBI
34	Cai L, Zhang G, Tong X, You Q, An Y, Wang Y, Guo L, Wang T, Zhu D and Zheng J: Growth inhibition of human ovarian cancer cells by blocking STAT3 activation with small interfering RNA. Eur J Obstet Gynecol Reprod Biol. 148:73–80. 2010. View Article : Google Scholar : PubMed/NCBI
35	Cattaneo F, Parisi M and Ammendola R: WKYMVm-induced cross-talk between FPR2 and HGF receptor in human prostate epithelial cell line PNT1A. FEBS Lett. 587:1536–1542. 2013. View Article : Google Scholar : PubMed/NCBI
36	Kam AY, Liu AM and Wong YH: Formyl peptide-receptor like-1 requires lipid raft and extracellular signal-regulated protein kinase to activate inhibitor-kappa B kinase in human U87 astrocytoma cells. J Neurochem. 103:1553–1566. 2007. View Article : Google Scholar : PubMed/NCBI
37	Manzano RG, Montuenga LM, Dayton M, Dent P, Kinoshita I, Vicent S, Gardner GJ, Nguyen P, Choi YH, Trepel J, et al: CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential. Oncogene. 21:4435–4447. 2002. View Article : Google Scholar : PubMed/NCBI
38	Kim D and Haynes CL: The role of p38 MAPK in neutrophil functions: Single cell chemotaxis and surface marker expression. Analyst. 138:6826–6833. 2013. View Article : Google Scholar : PubMed/NCBI
39	Park JT, Li M, Nakayama K, Mao TL, Davidson B, Zhang Z, Kurman RJ, Eberhart CG, Shih IeM and Wang TL: Notch3 gene amplification in ovarian cancer. Cancer Res. 66:6312–6318. 2006. View Article : Google Scholar : PubMed/NCBI