Browse > Article
http://dx.doi.org/10.5230/jgc.2014.14.3.196

Expression Levels of Vascular Endothelial Growth Factors A and C in Patients with Peptic Ulcers and Gastric Cancer  

Taghizadeh, Shirin (Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences)
Sankian, Mojtaba (Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences)
Ajami, Abolghasem (Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences)
Tehrani, Mohsen (Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences)
Hafezi, Nasim (Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences)
Mohammadian, Rajeeh (Department of Immunology, Faculty of Medicine, Mazandaran University of Medical Sciences)
Farazmandfar, Touraj (Faculty of Advanced Medical Science Technology, Golestan University of Medical Sciences)
Hosseini, Vahid (Inflammatory Diseases of Upper GI Tract Research Center, Mazandaran University of Medical Sciences)
Abbasi, Ali (Department of Pathology, Islamic Azad University)
Ajami, Maryam (Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences)
Publication Information
Journal of Gastric Cancer / v.14, no.3, 2014 , pp. 196-203 More about this Journal
Abstract
Purpose: Vascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels. Materials and Methods: Patients with dyspepsia who needed diagnostic endoscopy were selected and divided into three groups: nonulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction. Results: The VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance. Conclusions: Up-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.
Keywords
Vascular endothelial growth factor-A; Vascular endothelial growth factor-C; Stomach neoplasms; Peptic ulcer; Helicobacter pylori;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Selgrad M, Bornschein J, Rokkas T, Malfertheiner P. Clinical aspects of gastric cancer and Helicobacter pylori--screening, prevention, and treatment. Helicobacter 2010;15 Suppl 1:40-45.   DOI
2 Mokrowiecka A, Jurek K, Pińkowski D, Malecka-Panas E. The comparison of Health-Related Quality of Life (HRQL) in patients with GERD, peptic ulcer disease and ulcerative colitis. Adv Med Sci 2006;51:142-147.
3 Houghton J, Wang TC. Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers. Gastroenterology 2005;128:1567-1578.   DOI   ScienceOn
4 Rad R, Dossumbekova A, Neu B, Lang R, Bauer S, Saur D, et al. Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection. Gut 2004;53:1082-1089.   DOI   ScienceOn
5 Portal-Celhay C, Perez-Perez GI. Immune responses to Helicobacter pylori colonization: mechanisms and clinical outcomes. Clin Sci (Lond) 2006;110:305-314.   DOI
6 McColm JR, Geisen P, Hartnett ME. VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations between hyperoxia and hypoxia: relevance to clinical ROP. Mol Vis 2004;10:512-520.
7 Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 2004;56:549-580.   DOI   ScienceOn
8 de Paulis A, Prevete N, Fiorentino I, Rossi FW, Staibano S, Montuori N, et al. Expression and functions of the vascular endothelial growth factors and their receptors in human basophils. J Immunol 2006;177:7322-7331.   DOI
9 Yuanming L, Feng G, Lei T, Ying W. Quantitative analysis of lymphangiogenic markers in human gastroenteric tumor. Arch Med Res 2007;38:106-112.   DOI
10 Liu XE, Sun XD, Wu JM. Expression and significance of VEGF-C and FLT-4 in gastric cancer. World J Gastroenterol 2004;10:352-355.   DOI
11 Oshima H, Ishikawa T, Yoshida GJ, Naoi K, Maeda Y, Naka K, et al. TNF-$\alpha$/TNFR1 signaling promotes gastric tumorigenesis through induction of Noxo1 and Gna14 in tumor cells. Oncogene 2014;33:3820-3829.   DOI
12 Angelo LS, Kurzrock R. Vascular endothelial growth factor and its relationship to inflammatory mediators. Clin Cancer Res 2007;13:2825-2830.   DOI   ScienceOn
13 Strowski MZ, Cramer T, Schafer G, Juttner S, Walduck A, Schipani E, et al. Helicobacter pylori stimulates host vascular endothelial growth factor-A (vegf-A) gene expression via MEK/ERK-dependent activation of Sp1 and Sp3. FASEB J 2004;18:218-220.   DOI
14 Karkkainen MJ, Petrova TV. Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene 2000;19:5598-5605.   DOI   ScienceOn
15 Unemori EN, Ferrara N, Bauer EA, Amento EP. Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. J Cell Physiol 1992;153:557-562.   DOI
16 Lee J, Gray A, Yuan J, Luoh SM, Avraham H, Wood WI. Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. Proc Natl Acad Sci U S A 1996;93:1988-1992.   DOI   ScienceOn
17 Ishikawa M, Kitayama J, Kazama S, Nagawa H. Expression of vascular endothelial growth factor C and D (VEGF-C and -D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinoma. Jpn J Clin Oncol 2003;33:21-27.   DOI   ScienceOn
18 Lee HS, Kim J. Constitutive expression of vascular endothelial cell growth factor (VEGF) gene family ligand and receptors on human upper and lower airway epithelial cells. Int Forum Allergy Rhinol 2014;4:8-14.   DOI
19 Neuchrist C, Erovic BM, Handisurya A, Fischer MB, Steiner GE, Hollemann D, et al. Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck. Head Neck 2003;25:464-474.   DOI   ScienceOn
20 Tsurusaki T, Kanda S, Sakai H, Kanetake H, Saito Y, Alitalo K, et al. Vascular endothelial growth factor-C expression in human prostatic carcinoma and its relationship to lymph node metastasis. Br J Cancer 1999;80:309-313.   DOI   ScienceOn
21 Kitadai Y, Amioka T, Haruma K, Tanaka S, Yoshihara M, Sumii K, et al. Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas. Int J Cancer 2001;93:662-666.   DOI   ScienceOn
22 Hashimoto I, Kodama J, Seki N, Hongo A, Yoshinouchi M, Okuda H, et al. Vascular endothelial growth factor-C expression and its relationship to pelvic lymph node status in invasive cervical cancer. Br J Cancer 2001;85:93-97.   DOI   ScienceOn
23 Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 1996;2:1096-1103.   DOI   ScienceOn
24 Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev 1997;18:4-25.   DOI
25 Tian WY, Chen WC, Li R, Liu L. Markers CD40, VEGF, AKT, PI3K, and S100 correlate with tumor stage in gastric cancer. Onkologie 2013;36:26-31.   DOI
26 Melder RJ, Koenig GC, Witwer BP, Safabakhsh N, Munn LL, Jain RK. During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium. Nat Med 1996;2:992-997.   DOI
27 Jones MK, Kawanaka H, Baatar D, Szabó IL, Tsugawa K, Pai R, et al. Gene therapy for gastric ulcers with single local injection of naked DNA encoding VEGF and angiopoietin-1. Gastroenterology 2001;121:1040-1047.   DOI   ScienceOn
28 George ML, Tutton MG, Janssen F, Arnaout A, Abulafi AM, Eccles SA, et al. VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. Neoplasia 2001;3:420-427.   DOI   ScienceOn
29 Tsugawa H, Suzuki H, Saya H, Hatakeyama M, Hirayama T, Hirata K, et al. Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells. Cell Host Microbe 2012;12:764-777.   DOI
30 Ajami A, Shadman M, Rafiei A, Hosseini V, TalebiBezmin Abadi A, Alizadeh A, et al. Prevalence of EPIYA motifs in Helicobacter pylori strains isolated from patients with gastroduodenal disorders in northern Iran. Res Mol Med 2013;1:30-35.
31 Kondo K, Kaneko T, Baba M, Konno H. VEGF-C and VEGFA synergistically enhance lymph node metastasis of gastric cancer. Biol Pharm Bull 2007;30:633-637.   DOI   ScienceOn
32 Karpanen T, Egeblad M, Karkkainen MJ, Kubo H, Yla-Herttuala S, Jaattela M, et al. Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res 2001;61:1786-1790.
33 Amieva MR, El-Omar EM. Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology 2008;134:306-323.   DOI   ScienceOn
34 Zhang H, Wu J, Meng L, Shou CC. Expression of vascular endothelial growth factor and its receptors KDR and Flt-1 in gastric cancer cells. World J Gastroenterol 2002;8:994-998.   DOI
35 Wang X, Chen X, Fang J, Yang C. Overexpression of both VEGF-A and VEGF-C in gastric cancer correlates with prognosis, and silencing of both is effective to inhibit cancer growth. Int J Clin Exp Pathol 2013;6:586-597.
36 Chu SC, Tsai CH, Yang SF, Huang FM, Su YF, Hsieh YS, et al. Induction of vascular endothelial growth factor gene expression by proinflammatory cytokines in human pulp and gingival fibroblasts. J Endod 2004;30:704-707.   DOI
37 Brower V. Feeding the flame: new research adds to role of inflammation in cancer development. J Natl Cancer Inst 2005;97:251-253.   DOI