open access

Vol 88, No 10 (2017)
Research paper
Published online: 2017-10-31
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Mig-7 expression and vasculogenic mimicry in malignant ovarian tumors

Artur Czekierdowski1, Sylwia Czekierdowska1, Norbert Stachowicz2, Tomasz Łoziński3, Grzegorz Gurynowicz4
·
Pubmed: 29192416
·
Ginekol Pol 2017;88(10):552-561.
Affiliations
  1. Department of Gynecological Oncology and Gynecology, Staszica 16, 20-081 Lublin, Poland
  2. Department of Epidemiology and Clinical Research Methodology, ul.Chodźki 1, 20-093 Lublin, Poland
  3. Department of Obstetrics and Gynecology ,Pro Familia Hospital, ul.Witolda 6B, 35-302 Rzeszów, Poland
  4. Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Polna St. 33, 60-535 Poznań, Poland

open access

Vol 88, No 10 (2017)
ORIGINAL PAPERS Gynecology
Published online: 2017-10-31

Abstract

Objectives: To investigate the possible association of vasculogenic mimicry (VM), VE-cadherin and MIG-7 expression with clinicopathological features of women with malignant ovarian masses.

Material and methods: VM was studied with the PAS reaction and VE-cadherin was assessed with immunohistochemistry in 108 women with malignant ovarian tumors. Additionally, quantitative expression of MIG-7 mRNA was performed in 52 ovarian cancers with qRT-PCR.

Results: VM was found in 48/108 cases (44%), more often in higher FIGO stage tumors (83% cases; 40 vs. 8; p = 0.01). High expression of VE-cadherin was present in 37% of all ovarian masses. Ovarian tumors without VM more often expressed low levels of VE-cadherin than tumors where VM was found (37.6% vs.14.6%). No expression or very low expression of MIG-7 mRNA was found in all normal ovarian tissues and in 32 cancer samples. Median RQ of MIG-7 mRNA in tumor samples was higher than in normal ovarian tissue (RQ = 0.29 vs. RQ = 0.05, respectively; p < 0.005) and higher than in non-malignant ovarian masses (0.98 vs. 0.05 respectively; p = 0.03). Expression of MIG-7 mRNA was significantly correlated with VM (p = 0.039). In tumors with PAS-positive structures median RQ MIG-7 mRNA was higher than in tumors with PAS-negative findings (1.89 vs. 0.13 respectively). VE-cadherin expression was more frequently found in tumors where MIG-7 mRNA was present (p = 0.004).

Conclusions: Vasculogenic mimicry exists in malignant ovarian tumors and advanced clinical stages of malignancy are accompanied by a high incidence of VM formation. MIG-7 mRNA and VE-cadherin expression may serve as additional molecular markers of VM in ovarian malignancies.

Abstract

Objectives: To investigate the possible association of vasculogenic mimicry (VM), VE-cadherin and MIG-7 expression with clinicopathological features of women with malignant ovarian masses.

Material and methods: VM was studied with the PAS reaction and VE-cadherin was assessed with immunohistochemistry in 108 women with malignant ovarian tumors. Additionally, quantitative expression of MIG-7 mRNA was performed in 52 ovarian cancers with qRT-PCR.

Results: VM was found in 48/108 cases (44%), more often in higher FIGO stage tumors (83% cases; 40 vs. 8; p = 0.01). High expression of VE-cadherin was present in 37% of all ovarian masses. Ovarian tumors without VM more often expressed low levels of VE-cadherin than tumors where VM was found (37.6% vs.14.6%). No expression or very low expression of MIG-7 mRNA was found in all normal ovarian tissues and in 32 cancer samples. Median RQ of MIG-7 mRNA in tumor samples was higher than in normal ovarian tissue (RQ = 0.29 vs. RQ = 0.05, respectively; p < 0.005) and higher than in non-malignant ovarian masses (0.98 vs. 0.05 respectively; p = 0.03). Expression of MIG-7 mRNA was significantly correlated with VM (p = 0.039). In tumors with PAS-positive structures median RQ MIG-7 mRNA was higher than in tumors with PAS-negative findings (1.89 vs. 0.13 respectively). VE-cadherin expression was more frequently found in tumors where MIG-7 mRNA was present (p = 0.004).

Conclusions: Vasculogenic mimicry exists in malignant ovarian tumors and advanced clinical stages of malignancy are accompanied by a high incidence of VM formation. MIG-7 mRNA and VE-cadherin expression may serve as additional molecular markers of VM in ovarian malignancies.

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Keywords

ovarian cancer, Mig-7,VE-cadherin, vasculogenic mimicry

About this article
Title

Mig-7 expression and vasculogenic mimicry in malignant ovarian tumors

Journal

Ginekologia Polska

Issue

Vol 88, No 10 (2017)

Article type

Research paper

Pages

552-561

Published online

2017-10-31

Page views

1506

Article views/downloads

1334

DOI

10.5603/GP.a2017.0100

Pubmed

29192416

Bibliographic record

Ginekol Pol 2017;88(10):552-561.

Keywords

ovarian cancer
Mig-7
VE-cadherin
vasculogenic mimicry

Authors

Artur Czekierdowski
Sylwia Czekierdowska
Norbert Stachowicz
Tomasz Łoziński
Grzegorz Gurynowicz

References (33)
  1. Siegel RL, Miller KD, Fedewa SA, et al. Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1): 7–30.
  2. Ricci F, Guffanti F, Damia G, et al. Combination of paclitaxel, bevacizumab and MEK162 in second line treatment in platinum-relapsing patient derived ovarian cancer xenografts. Mol Cancer. 2017; 16(1): 97.
  3. Ren F, Shen J, Shi H, et al. Novel mechanisms and approaches to overcome multidrug resistance in the treatment of ovarian cancer. Biochim Biophys Acta. 2016; 1866(2): 266–275.
  4. Markowska A, Sajdak S, Markowska J, et al. Angiogenesis and cancer stem cells: New perspectives on therapy of ovarian cancer. Eur J Med Chem. 2017 [Epub ahead of print].
  5. Schmid BC, Oehler MK. New perspectives in ovarian cancer treatment. Maturitas. 2014; 77(2): 128–136.
  6. Hollingsworth HC, Kohn EC, Steinberg SM, et al. Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol. 1995; 147(1): 33–41.
  7. Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol. 1999; 155(3): 739–752.
  8. Sood AK, Seftor EA, Fletcher MS, et al. Molecular determinants of ovarian cancer plasticity. Am J Pathol. 2001; 158(4): 1279–1288.
  9. Folberg R, Hendrix MJ, Maniotis AJ. Vasculogenic mimicry and tumor angiogenesis. Am J Pathol. 2000; 156(2): 361–381.
  10. Czekierdowska S, Stachowicz N, Chróściel M, et al. Proliferation and maturation of intratumoral blood vessels in women with malignant ovarian tumors assessed with cancer stem cells marker nestin and platelet derived growth factor PDGF-B. Ginekol Pol. 2017; 88(3): 120–128.
  11. Martin TA, Harding K, Jiang WG. Matrix-bound fibroblasts regulate angiogenesis by modulation of VE-cadherin. Eur J Clin Invest. 2001; 31(11): 931–938.
  12. Hendrix MJC, Seftor EA, Hess AR, et al. Molecular plasticity of human melanoma cells. Oncogene. 2003; 22(20): 3070–3075.
  13. Aragon-Sanabria V, Pohler SE, Eswar VJ, et al. VE-Cadherin Disassembly and Cell Contractility in the Endothelium are Necessary for Barrier Disruption Induced by Tumor Cells. Sci Rep. 2017; 7: 45835.
  14. Haidari M, Zhang W, Wakame K. Disruption of endothelial adherens junction by invasive breast cancer cells is mediated by reactive oxygen species and is attenuated by AHCC. Life Sci. 2013; 93(25-26): 994–1003.
  15. Crouch S, Spidel CS, Lindsey JS. HGF and ligation of alphavbeta5 integrin induce a novel, cancer cell-specific gene expression required for cell scattering. Exp Cell Res. 2004; 292(2): 274–287.
  16. Phillips TM, Lindsey JS. Carcinoma cell-specific Mig-7: a new potential marker for circulating and migrating cancer cells. Oncol Rep. 2005; 13(1): 37–44.
  17. Petty AP, Garman KL, Winn VD, et al. Overexpression of carcinoma and embryonic cytotrophoblast cell-specific Mig-7 induces invasion and vessel-like structure formation. Am J Pathol. 2007; 170(5): 1763–1780.
  18. Ho MY, Hung SW, Liang CM, et al. Recombinant viral capsid protein VP1 suppresses lung cancer metastasis by inhibiting COX-2/PGE2 and MIG-7. Oncotarget. 2014; 5(11): 3931–3943.
  19. Robertson GP. Mig-7 linked to vasculogenic mimicry. Am J Pathol. 2007; 170(5): 1454–1456.
  20. Petty AP, Wright SE, Rewers-Felkins KA, et al. Targeting migration inducting gene-7 inhibits carcinoma cell invasion, early primary tumor growth, and stimulates monocyte oncolytic activity. Mol Cancer Ther. 2009; 8(8): 2412–2423.
  21. Huang B, Yin M, Li X, et al. Migration-inducing gene 7 promotes tumorigenesis and angiogenesis and independently predicts poor prognosis of epithelial ovarian cancer. Oncotarget. 2016; 7(19): 27552–27566.
  22. Hendrix MJ, Seftor EA, Meltzer PS, et al. Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry. Proc Natl Acad Sci U S A. 2001; 98(14): 8018–8023.
  23. Alvero AB, Fu HH, Holmberg J, et al. Stem-like ovarian cancer cells can serve as tumor vascular progenitors. Stem Cells. 2009; 27(10): 2405–2413.
  24. Wang JY, Sun T, Zhao XL, et al. Functional significance of VEGF-a in human ovarian carcinoma: role in vasculogenic mimicry. Cancer Biol Ther. 2008; 7(5): 758–766.
  25. Liao S, Gao Q. [Expressions and clinical significance of vasculogenic mimicry and related protein Mig-7 and MMP-2 in gastric carcinoma]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2013; 29(2): 194–196.
  26. Fan YZ, Sun W. Molecular regulation of vasculogenic mimicry in tumors and potential tumor-target therapy. World J Gastrointest Surg. 2010; 2(4): 117–127.
  27. Farina HG, Pomies M, Alonso DF, et al. Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncol Rep. 2006; 16(4): 885–891.
  28. Cong R, Sun Q, Yang Li, et al. Effect of Genistein on vasculogenic mimicry formation by human uveal melanoma cells. J Exp Clin Cancer Res. 2009; 28: 124.
  29. Itzhaki O, Greenberg E, Shalmon B, et al. Nicotinamide inhibits vasculogenic mimicry, an alternative vascularization pathway observed in highly aggressive melanoma. PLoS One. 2013; 8(2): e57160.
  30. Tapaneeyakorn S, Chantima W, Thepthai C, et al. Production, characterization, and in vitro effects of a novel monoclonal antibody against Mig-7. Biochem Biophys Res Commun. 2016; 475(2): 149–153.
  31. Karakaya BK, Başer E, Bildacı B, et al. Alternative tumor markers in the diagnosis of ovarian cancer. Ginekol Pol. 2016; 87(8): 565–769.
  32. Zhang M, Zhuang G, Sun X, et al. Risk prediction model for epithelial ovarian cancer using molecular markers and clinical characteristics. J Ovarian Res. 2015; 8: 67.
  33. Delgado-Bellido D, Serrano-Saenz S, Fernández-Cortés M, et al. Vasculogenic mimicry signaling revisited: focus on non-vascular VE-cadherin. Mol Cancer. 2017; 16(1): 65.

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