Expression and clinical significance of focal adhesion kinase and adrenomedullin in epithelial ovarian cancer

Li,Mingqun; Hong,Li; Liao,Meimei; Guo,Guanglin

doi:10.3892/ol.2015.3278

Expression and clinical significance of focal adhesion kinase and adrenomedullin in epithelial ovarian cancer

Authors:
- Mingqun Li
- Li Hong
- Meimei Liao
- Guanglin Guo
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Affiliations: Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, P.R. China, Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, Hubei 430000, P.R. China
Published online on: May 27, 2015 https://doi.org/10.3892/ol.2015.3278
Pages: 1003-1007

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Abstract

The aim of the present study was to investigate the expression of focal adhesion kinase (FAK) and adrenomedullin (ADM) and determine their clinical significance and cooperative role in human epithelial ovarian cancer. The expression of FAK and ADM was investigated in epithelial ovarian cancer, benign ovarian tumors and normal control tissues by immunohistochemical staining and optical microscopy. The FAK and ADM expression and correlation with clinicopathological parameters was analyzed using SPSS 13.0 software. The expression of FAK and ADM in epithelial ovarian cancer was significantly higher compared with that in benign tumors or normal ovarian tissues (P<0.01); however, no significant difference was observed between benign tumors and normal tissues (P>0.05). The expression of FAK was found to be correlated with histological grade, clinical stage, lymph node metastasis and prognosis (P<0.05), but exhibited no significant association with patient age or histological type (P>0.05). The expression of ADM was significantly correlated with pathological grade, lymph node metastasis and prognosis (P<0.05), but not with age, clinical stage or histological type (P>0.05). The Spearman's rank correlation analysis revealed a positive correlation between FAK and ADM expression (r=0.314). FAK and ADM were more highly expressed in epithelial ovarian cancer compared with benign tumors or normal ovarian tissues. Furthermore, FAK and ADM may play a cooperative role; specifically, FAK may upregulate ADM in the invasion and migration of epithelial ovarian cancer. Thus, FAK and ADM may represent potential biomarkers for evaluating the malignant potential and prognosis of ovarian cancer.

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1	Morgan RJ Jr, Alvarez RD, Armstrong DK, Boston B, Burger RA, Chen LM, Copeland L, Crispens MA, Gershenson D, Gray HJ, et al: National Comprehensive Cancer Network: Epithelial ovarian cancer. J Natl Compr Canc Netw. 9:82–113. 2011.PubMed/NCBI
2	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar : PubMed/NCBI
3	Colombo N, Peiretti M, Parma G, et al: Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 21:v23–v30. 2010. View Article : Google Scholar : PubMed/NCBI
4	Baron V, Calléja V, Ferrari P, Alengrin F and Van Obberghen E: p125Fak focal adhesion kinase is a substrate for the insulin and insulin-like growth factor-I tyrosine kinase receptors. J Biol Chem. 273:7162–7168. 1998. View Article : Google Scholar : PubMed/NCBI
5	McLean GW, Carragher NO, Avizienyte E, Evans J, Brunton VG and Frame MC: The role of focal-adhesion kinase in cancer - a new therapeutic opportunity. Nat Rev Cancer. 5:505–515. 2005. View Article : Google Scholar : PubMed/NCBI
6	Nikitenko LL, Leek R, Henderson S, et al: The G-protein-coupled receptor CLR is upregulated in an autocrine loop with adrenomedullin in clear cell renal cell carcinoma and associated with poor prognosis. Clin Cancer Res. 19:5740–5748. 2013. View Article : Google Scholar : PubMed/NCBI
7	Halder J, Landen CN, Lutgendorf SK, et al: Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells. Clin Cancer Res. 11:8829–8836. 2005. View Article : Google Scholar : PubMed/NCBI
8	Huang YT, Lee LT, Lee PP, Lin YS and Lee MT: Targeting of focal adhesion kinase by flavonoids and small-interfering RNAs reduces tumor cell migration ability. Anticancer Res. 25:2017–2025. 2005.PubMed/NCBI
9	Gao M, Liu X, Sun H, Ren H, Wang L and Shen Y: Study on FAK regulation of migration of vascular endothelial cells depending upon focal adhesion proteins. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 30:567–571. 2013.(In Chinese). PubMed/NCBI
10	Grisaru-Granovsky S, Salah Z, Maoz M, Pruss D, Beller U and Bar-Shavit R: Differential expression of protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples. Int J Cancer. 113:372–378. 2005. View Article : Google Scholar : PubMed/NCBI
11	Saldanha SN and Tollefsbol TO: Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis. J Cell Physiol. 229:393–406. 2014. View Article : Google Scholar : PubMed/NCBI
12	Sood AK, Coffin JE, Schneider GB, Fletcher MS, DeYoung BR, Gruman LM, Gershenson DM, Schaller MD and Hendrix MJ: Biological significance of focal adhesion kinase in ovarian cancer: role in migration and invasion. Am J Pathol. 165:1087–1095. 2004. View Article : Google Scholar : PubMed/NCBI
13	Judson PL, He X, Cance WG and Van Le L: Overexpression of focal adhesion kinase, a protein tyrosine kinase, in ovarian carcinoma. Cancer. 15:1551–1556. 1999. View Article : Google Scholar
14	Frede S, Freitag P, Otto T, Heilmaier C and Fandrey J: The proinflammatory cytokine interleukin 1beta and hypoxia cooperatively induce the expression of adrenomedullin in ovarian carcinoma cells through hypoxia inducible factor 1 activation. Cancer Res. 65:4690–4697. 2005. View Article : Google Scholar : PubMed/NCBI
15	Cuttitta F, Pío R, Garayoa M, Zudaire E, Julián M, Elsasser TH, Montuenga LM and Martínez A: Adrenomedullin functions as an important tumor survival factor in human carcinogenesis. Microsc Res Tech. 57:110–119. 2002. View Article : Google Scholar : PubMed/NCBI
16	Zudaire E, Martinez A and Cuttitta F: Adrenomedullin and cancer. Regul Pept. 112:175–183. 2003. View Article : Google Scholar : PubMed/NCBI
17	Pang X, Shang H, Deng B, Wen F and Zhang Y: The Interaction of Adrenomedullin and Macrophages Induces Ovarian Cancer Cell Migration via Activation of RhoA Signaling Pathway. Int J Mol Sci. 14:2774–2787. 2013. View Article : Google Scholar : PubMed/NCBI
18	Provenzano PP and Keely PJ: The role of focal adhesion kinase in tumor initiation and progression. Cell Adh Migr. 3:347–350. 2009. View Article : Google Scholar : PubMed/NCBI
19	Karpinich NO, Hoopes SL, Kechele DO, Lenhart PM and Caron KM: Adrenomedullin function in vascular endothelial cells: Insights from genetic mouse models. Curr Hypertens Rev. 7:228–239. 2011. View Article : Google Scholar : PubMed/NCBI
20	Zudaire E, Martínez A, Garayoa M, Pío R, Kaur G, Woolhiser MR, Metcalfe DD, Hook WA, Siraganian RP, Guise TA, et al: Adrenomedullin is a cross-talk molecule that regulates tumor and mast cell function during human carcinogenesis. Am J Pathol. 168:280–291. 2006. View Article : Google Scholar : PubMed/NCBI