Effects of HCG on human epithelial ovarian cancer vasculogenic mimicry formation in vivo

Gao,Sainan; Fan,Chao; Huang,Hua; Zhu,Changlai; Su,Min; Zhang,Yuquan

doi:10.3892/ol.2016.4630

Effects of HCG on human epithelial ovarian cancer vasculogenic mimicry formation in vivo

Authors:
- Sainan Gao
- Chao Fan
- Hua Huang
- Changlai Zhu
- Min Su
- Yuquan Zhang
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Affiliations: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Electron Microscopy, Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: May 25, 2016 https://doi.org/10.3892/ol.2016.4630
Pages: 459-466
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer is the leading cause of mortality due to gynecological malignancy, and vasculogenic mimicry (VM) formation is correlated with poor prognosis. In a previous study, the present authors observed that human chorionic gonadotropin (HCG) could promote VM formation in three‑dimensional OVCAR‑3 cell cultures. In order to investigate whether HCG could promote VM formation in ovarian cancer in vivo, the role of OVCAR‑3 cells overexpressing or depleted of chorionic gonadotropin, beta polypeptide 5 (CGB5, which is the fifth subunit of β‑HCG and was identified as the key part of HCG) were injected into nude mice in the present study, while BeWo cells were used as a positive control. The results demonstrated that overexpressed CGB5 promoted xenografts tumor formation in nude mice, and the results of hematoxylin and eosin and cluster of differentiation (CD)34‑periodic acid‑Schiff dual staining revealed that CGB5 promoted VM formation. Furthermore, reverse transcription-polymerase chain reaction and immunochemistry staining demonstrated that the expression of the vascular markers CD31, vascular endothelial growth factor and factor VIII was also upregulated in the CGB5-overexpressing xenografts tumors. In addition, the expression of luteinizing hormone receptor (LHR), the receptor of CGB5, was increased in CGB5-overexpressing cells. In conclusion, CGB5 may promote tumor growth and VM formation via activation of the LHR signal transduction pathway, which may support a novel strategy for ovarian cancer therapy.

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1	Zhang B, Barekati Z, Kohler C, Radpour R, Asadollahi R, Holzgreve W and Zhong XY: Proteomics and biomarkers for ovarian cancer diagnosis. Ann Clin Lab Sci. 40:218–225. 2010.PubMed/NCBI
2	Wang JY, Sun T, Zhao XL, Zhang SW, Zhang DF, Gu Q, Wang XH, Zhao N, Qie S and Sun BC: Functional significance of VEGF-a in human ovarian carcinoma: Role in vasculogenic mimicry. Cancer Biol Ther. 7:758–766. 2008. View Article : Google Scholar : PubMed/NCBI
3	Zhang S, Zhang D and Sun B: Vasculogenic mimicry: Current status and future prospects. Cancer Lett. 254:157–164. 2007. View Article : Google Scholar : PubMed/NCBI
4	Vartanian AA, Burova OS, Stepanova EV, Baryshnikov AY and Lichinitser MR: Melanoma vasculogenic mimicry is strongly related to reactive oxygen species level. Melanoma Res. 17:370–379. 2007. View Article : Google Scholar : PubMed/NCBI
5	Folkman J: Fundamental concepts of the angiogenic process. Curr Mol Med. 3:643–651. 2003. View Article : Google Scholar : PubMed/NCBI
6	Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe'er J, Trent JM, Meltzer PS and Hendrix MJ: Vascular channel formation by human melanoma cells in vivo and in vitro: Vasculogenic mimicry. Am J Pathol. 155:739–752. 1999. View Article : Google Scholar : PubMed/NCBI
7	Sun W, Fan YZ, Zhang WZ and Ge CY: A pilot histomorphology and hemodynamic of vasculogenic mimicry in gallbladder carcinomas in vivo and in vitro. J Exp Clin Cancer Res. 30:462011. View Article : Google Scholar : PubMed/NCBI
8	Hess AR, Seftor EA, Seftor RE and Hendrix MJ: Phosphoinositide 3-kinase regulates membrane Type 1-matrix metalloproteinase (MMP) and MMP-2 activity during melanoma cell vasculogenic mimicry. Cancer Res. 63:4757–4762. 2003.PubMed/NCBI
9	Sun B, Zhang D, Zhang S, Zhang W, Guo H and Zhao X: Hypoxia influences vasculogenic mimicry channel formation and tumor invasion-related protein expression in melanoma. Cancer Lett. 249:188–197. 2007. View Article : Google Scholar : PubMed/NCBI
10	Sood AK, Seftor EA, Fletcher MS, Gardner LM, Heidger PM, Buller RE, Seftor RE and Hendrix MJ: Molecular determinants of ovarian cancer plasticity. Am J Pathol. 158:1279–1288. 2001. View Article : Google Scholar : PubMed/NCBI
11	Shirakawa K, Wakasugi H, Heike Y, Watanabe I, Yamada S, Saito K and Konishi F: Vasculogenic mimicry and pseudo-comedo formation in breast cancer. Int J Cancer. 99:821–828. 2002. View Article : Google Scholar : PubMed/NCBI
12	Guzman G, Cotler SJ, Lin AY, Maniotis AJ and Folberg R: A pilot study of vasculogenic mimicry immunohistochemical expression in hepatocellular carcinoma. Arch Pathol Lab Med. 131:1776–1781. 2007.PubMed/NCBI
13	Sharma N, Seftor RE, Seftor EA, Gruman LM, Heidger PM Jr, Cohen MB, Lubaroff DM and Hendrix MJ: Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: Role in vasculogenic mimicry. Prostate. 50:189–201. 2002. View Article : Google Scholar : PubMed/NCBI
14	Vartanian AA, Stepanova EV, Gutorov SL, Solomko ESh, Grigorieva IN, Sokolova IN, Baryshnikov AY and Lichinitser MR: Prognostic significance of periodic acid-Schiff-positive patterns in clear cell renal cell carcinoma. Can J Urol. 16:4726–4732. 2009.PubMed/NCBI
15	El Hallani S, Boisselier B, Peglion F, Rousseau A, Colin C, Idbaih A, Marie Y, Mokhtari K, Thomas JL, Eichmann A, et al: A new alternative mechanism in glioblastoma vascularization: Tubular vasculogenic mimicry. Brain. 133:973–982. 2010. View Article : Google Scholar : PubMed/NCBI
16	Li M, Gu Y, Zhang Z, Zhang S, Zhang D, Saleem AF, Zhao X and Sun B: Vasculogenic mimicry: A new prognostic sign of gastric adenocarcinoma. Pathol Oncol Res. 16:259–266. 2010. View Article : Google Scholar : PubMed/NCBI
17	Baeten CI, Hillen F, Pauwels P, de Bruine AP and Baeten CG: Prognostic role of vasculogenic mimicry in colorectal cancer. Dis Colon Rectum. 52:2028–2035. 2009. View Article : Google Scholar : PubMed/NCBI
18	Shih IeM: Trophoblastic vasculogenic mimicry in gestational choriocarcinoma. Mod Pathol. 24:646–652. 2011. View Article : Google Scholar : PubMed/NCBI
19	Sood AK, Fletcher MS, Zahn CM, Gruman LM, Coffin JE, Seftor EA and Hendrix MJ: The clinical significance of tumor cell-lined vasculature in ovarian carcinoma: Implications for anti-vasculogenic therapy. Cancer Biol Ther. 1:661–664. 2002. View Article : Google Scholar : PubMed/NCBI
20	Zygmunt M, Herr F, Keller-Schoenwetter S, Kunzi-Rapp K, Münstedt K, Rao CV, Lang U and Preissner KT: Characterization of human chorionic gonadotropin as a novel angiogenic factor. J Clin Endocrinol Metab. 87:5290–5296. 2002. View Article : Google Scholar : PubMed/NCBI
21	Toth P, Li X, Rao CV, Lincoln SR, Sanfilippo JS, Spinnato JA II and Yussman MA: Expression of functional human chorionic gonadotropin/human luteinizing hormone receptor gene in human uterine arteries. J Clin Endocrinol Metab. 79:307–315. 1994. View Article : Google Scholar : PubMed/NCBI
22	Wulff C, Dickson SE, Duncan WC and Fraser HM: Angiogenesis in the human corpus luteum: Simulated early pregnancy by HCG treatment is associated with both angiogenesis and vessel stabilization. Hum Reprod. 16:2515–2524. 2001. View Article : Google Scholar : PubMed/NCBI
23	Berndt S, Perrier D'Hauterive S, Blacher S, Péqueux C, Lorquet S, Munaut C, Applanat M, Hervé MA, Lamandé N, Corvol P, et al: Angiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium. FASEB J. 20:2630–2632. 2006. View Article : Google Scholar : PubMed/NCBI
24	Michel RM, Aguilar JL and Arrieta O: Human chorionic gonadotropin as an angiogenic factor in breast cancer during pregnancy. Med Hypotheses. 68:1035–1040. 2007. View Article : Google Scholar : PubMed/NCBI
25	Szajnik M, Nowak-Markwitz E, Szczepański MJ and Spaczyński M: Assessment of expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LH/hCGR) and hCG protein in ovarian cancer tissues. Ginekol Pol. 78:939–943. 2007.(In Polish). PubMed/NCBI
26	Muller CY and Cole LA: The quagmire of hCG and hCG testing in gynecologic oncology. Gynecol Oncol. 112:663–672. 2009. View Article : Google Scholar : PubMed/NCBI
27	Lempiäinen A, Stenman UH, Blomqvist C and Hotakainen K: Free beta-subunit of human chorionic gonadotropin in serum is a diagnostically sensitive marker of seminomatous testicular cancer. Clin Chem. 54:1840–1843. 2008. View Article : Google Scholar : PubMed/NCBI
28	Iles RK, Delves PJ and Butler SA: Does hCG or hCGβ play a role in cancer cell biology? Mol Cell Endocrinol. 329:62–70. 2010. View Article : Google Scholar : PubMed/NCBI
29	Daniel KD, Kim GY, Vassiliou CC, Jalali-Yazdi F, Langer R and Cima MJ: Multi-reservoir device for detecting a soluble cancer biomarker. Lab Chip. 7:1288–1293. 2007. View Article : Google Scholar : PubMed/NCBI
30	Jankowska AG, Andrusiewicz M, Fischer N and Warchol PJ: Expression of hCG and GnRHs and their receptors in endometrial carcinoma and hyperplasia. Int J Gynecol Cancer. 20:92–101. 2010. View Article : Google Scholar : PubMed/NCBI
31	Su M, Wei W, Xu X, Wang X, Chen C, Su L and Zhang Y: Role of hCG in vasculogenic mimicry in OVCAR-3 ovarian cancer cell line. Int J Gynecol Cancer. 21:1366–1374. 2011. View Article : Google Scholar : PubMed/NCBI
32	Kavak S, Ayaz L and Emre M: Effects of rosiglitazone with insulin combination therapy on oxidative stress and lipid profile in left ventricular muscles of diabetic rats. Exp Diabetes Res. 2012:9056832012. View Article : Google Scholar : PubMed/NCBI
33	Newton PT, Staines KA, Spevak L, Boskey AL, Teixeira CC, Macrae VE, Canfield AE and Farquharson C: Chondrogenic ATDC5 cells: An optimised model for rapid and physiological matrix mineralisation. Int J Mol Med. 30:1187–1193. 2012.PubMed/NCBI
34	Scimeca M, Orlandi A, Terrenato I, Bischetti S and Bonanno E: Assessment of metal contaminants in non-small cell lung cancer by EDX microanalysis. Eur J Histochem. 58:24032014. View Article : Google Scholar : PubMed/NCBI
35	Brouillet S, Hoffmann P, Chauvet S, Salomon A, Chamboredon S, Sergent F, Benharouga M, Feige JJ and Alfaidy N: Revisiting the role of hCG: new regulation of the angiogenic factor EG-VEGF and its receptors. Cell Mol Life Sci. 69:1537–50. 2012. View Article : Google Scholar : PubMed/NCBI
36	Hamada AL, Nakabayashi K, Sato A, Kiyoshi K, Takamatsu Y, Laoag-Fernandez JB, Ohara N and Maruo T: Transfection of antisense chorionic gonadotropin beta gene into choriocarcinoma cells suppresses the cell proliferation and induces apoptosis. J Clin Endocrinol Metab. 90:4873–4879. 2005. View Article : Google Scholar : PubMed/NCBI
37	Bo M and Boime I: Identification of the transcriptionally active genes of the chorionic gonadotropin beta gene cluster in vivo. J Biol Chem. 267:3179–3184. 1992.PubMed/NCBI
38	Talmadge K, Boorstein WR, Vamvakopoulos NC, Gething MJ and Fiddes JC: Only three of the seven human chorionic gonadotropin beta subunit genes can be expressed in the placenta. Nucleic Acids Res. 12:8415–8436. 1984. View Article : Google Scholar : PubMed/NCBI
39	Meng XL, Rennert OM and Chan WY: Human chorionic gonadotropin induces neuronal differentiation of PC12 cells through activation of stably expressed lutropin/choriogonadotropin receptor. Endocrinology. 148:5865–5873. 2007. View Article : Google Scholar : PubMed/NCBI