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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
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Abstract
Objectives: Platelet-derived growth factor B (PDGF-B) and nestin have been suggested to be useful in the assessment of neoangiogenesis in malignant ovarian masses. We aimed to investigate a possible association of these markers with newly formed microcapillaries and perivascular cells in ovarian tumors.
Material and methods: Microvessel density (MVD) and pericytes were studied in 82 women with ovarian neoplasms, including 7 benign cysts, 7 borderline masses, 64 epithelial ovarian cancers and 4 other malignant ovarian tumors. Immunohistochemical staining included antibodies to CD34, PDGF-B and nestin.
Results: Median values of CD34-positive and nestin-positive MVD were: 24,5 (range:17-32) and 21 (range: 12–31), respectively. No significant correlation between intratumoral CD-34 positive MVD and nestin-positive MVD was found. Benign and borderline lesions more frequently than malignant tumors displayed low or medium values of nestin-positive MVD (p = 0.01). Histological grading of malignant tumors was associated with nestin-positive MVD (p = 0.01). Nestin expression in tumor cells was not correlated with tumor grade or histological subtype. PDGF-B expression was found in tumor microvessels in 72% of cases (59/82). High expression of PDGF in pericapillary cells was strongly associated with high expression of this marker in cancer cells (p = 0.007). Significant correlations between PDGF-B and nestin expression in malignant tumor microvessels were also found (p = 0.04). Nestin and PDGF-B expressions were strongly associated with high grade tumors when compared to low grade or benign masses.
Conclusions: We conclude that the assessment of PDGF-B and nestin-positive MVD could be used to identify only highly active, angiogenic malignant ovarian masses, where tumor vasculature is formed.
Abstract
Objectives: Platelet-derived growth factor B (PDGF-B) and nestin have been suggested to be useful in the assessment of neoangiogenesis in malignant ovarian masses. We aimed to investigate a possible association of these markers with newly formed microcapillaries and perivascular cells in ovarian tumors.
Material and methods: Microvessel density (MVD) and pericytes were studied in 82 women with ovarian neoplasms, including 7 benign cysts, 7 borderline masses, 64 epithelial ovarian cancers and 4 other malignant ovarian tumors. Immunohistochemical staining included antibodies to CD34, PDGF-B and nestin.
Results: Median values of CD34-positive and nestin-positive MVD were: 24,5 (range:17-32) and 21 (range: 12–31), respectively. No significant correlation between intratumoral CD-34 positive MVD and nestin-positive MVD was found. Benign and borderline lesions more frequently than malignant tumors displayed low or medium values of nestin-positive MVD (p = 0.01). Histological grading of malignant tumors was associated with nestin-positive MVD (p = 0.01). Nestin expression in tumor cells was not correlated with tumor grade or histological subtype. PDGF-B expression was found in tumor microvessels in 72% of cases (59/82). High expression of PDGF in pericapillary cells was strongly associated with high expression of this marker in cancer cells (p = 0.007). Significant correlations between PDGF-B and nestin expression in malignant tumor microvessels were also found (p = 0.04). Nestin and PDGF-B expressions were strongly associated with high grade tumors when compared to low grade or benign masses.
Conclusions: We conclude that the assessment of PDGF-B and nestin-positive MVD could be used to identify only highly active, angiogenic malignant ovarian masses, where tumor vasculature is formed.
Keywords
ovarian cancer, microvessel desity, nestin, PDGF, pericytes
About this articleTitle
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
Journal
Issue
Article type
Research paper
Pages
120-128
Published online
2017-03-31
Page views
1730
Article views/downloads
1955
DOI
Pubmed
Bibliographic record
Ginekol Pol 2017;88(3):120-128.
Keywords
ovarian cancer
microvessel desity
nestin
PDGF
pericytes
Authors
Sylwia Czekierdowska
Norbert Stachowicz
Mieczysław Chróściel
Artur Czekierdowski
References (27)- Folkman J, Ryeom S, Folkman J, et al. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990; 82(1): 4–6.
- Baluk P, Morikawa S, Haskell A, et al. Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol. 2002; 160(3): 985–1000.
- Bergers G, Song S, Meyer-Morse N, et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003; 111(9): 1287–1295.
- Hashizume H, Baluk P, Morikawa S, et al. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol. 2000; 156(4): 1363–1380.
- Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005; 307(5706): 58–62.
- Weidner N. Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol. 1995; 147(1): 9–19.
- Gómez-Raposo C, Mendiola M, Barriuso J, et al. Angiogenesis and ovarian cancer. Clin Transl Oncol. 2009; 11(9): 564–571.
- Matsuda Y, Hagio M, Ishiwata T. Nestin: a novel angiogenesis marker and possible target for tumor angiogenesis. World J Gastroenterol. 2013; 19(1): 42–48.
- Mokrý J, Cízková D, Filip S, et al. Nestin expression by newly formed human blood vessels. Stem Cells Dev. 2004; 13(6): 658–664.
- Aihara M, Sugawara Ki, Torii S, et al. Angiogenic endothelium-specific nestin expression is enhanced by the first intron of the nestin gene. Lab Invest. 2004; 84(12): 1581–1592.
- He QZ, Luo XZ, Zhou Q, et al. Expression of nestin in ovarian serous cancer and its clinicopathologic significance. Eur Rev Med Pharmacol Sci. 2013; 17(21): 2896–2901.
- Zhou N, Wu X, Yang Bo, et al. Stem cell characteristics of dormant cells and cisplatin‑induced effects on the stemness of epithelial ovarian cancer cells. Mol Med Rep. 2014; 10(5): 2495–2504.
- Klein D, Meissner N, Kleff V, et al. Nestin(+) tissue-resident multipotent stem cells contribute to tumor progression by differentiating into pericytes and smooth muscle cells resulting in blood vessel remodeling. Front Oncol. 2014; 4: 169.
- Qin Q, Sun Y, Fei M, et al. Expression of putative stem marker nestin and CD133 in advanced serous ovarian cancer. Neoplasma. 2012; 59(3): 310–315.
- Chen Z, Wang T, Luo H, et al. Expression of nestin in lymph node metastasis and lymphangiogenesis in non-small cell lung cancer patients. Hum Pathol. 2010; 41(5): 737–744.
- Hellström M, Kalén M, Lindahl P, et al. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development. 1999; 126(14): 3047–3055.
- Sá da Bandeira D, Casamitjana J, Crisan M. Pericytes, integral components of adult hematopoietic stem cell niches. Pharmacol Ther. 2017; 171: 104–113.
- Song S, Ewald AJ, Stallcup W, et al. PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol. 2005; 7(9): 870–879.
- Paulsson J, Ehnman M, Östman A. PDGF receptors in tumor biology: prognostic and predictive potential. Future Oncol. 2014; 10(9): 1695–1708.
- Osman WM, Shash LS, Ahmed NS. Emerging role of nestin as an angiogenesis and cancer stem cell marker in epithelial ovarian cancer: immunohistochemical study. Appl Immunohistochem Mol Morphol. 2016 [Epub ahead of print].
- Dong J, Zhao Y, Huang Q, et al. Glioma stem/progenitor cells contribute to neovascularization via transdifferentiation. Stem Cell Rev. 2011; 7(1): 141–152.
- Ben-Hamo R, Efroni S. Biomarker robustness reveals the PDGF network as driving disease outcome in ovarian cancer patients in multiple studies. BMC Syst Biol. 2012; 6: 3.
- Madsen CV, Steffensen KD, Olsen DA, et al. Serum platelet-derived growth factor and fibroblast growth factor in patients with benign and malignant ovarian tumors. Anticancer Res. 2012; 32(9): 3817–3825.
- Madsen CV, Steffensen KD, Olsen DA, et al. Serial measurements of serum PDGF-AA, PDGF-BB, FGF2, and VEGF in multiresistant ovarian cancer patients treated with bevacizumab. J Ovarian Res. 2012; 5(1): 23.
- Hosaka K, Yang Y, Seki T, et al. Pericyte-fibroblast transition promotes tumor growth and metastasis. Proc Natl Acad Sci U S A. 2016; 113(38): E5618–E5627.
- Klein D, Meissner N, Kleff V, et al. Nestin(+) tissue-resident multipotent stem cells contribute to tumor progression by differentiating into pericytes and smooth muscle cells resulting in blood vessel remodeling. Front Oncol. 2014; 4: 169.
- Lu C, Shahzad MMK, Moreno-Smith M, et al. Targeting pericytes with a PDGF-B aptamer in human ovarian carcinoma models. Cancer Biol Ther. 2010; 9(3): 176–182.
