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Comprehensive Analysis of Vascular Endothelial Growth Factor-C Related Factors in Stomach Cancer

  • Liu, Yong-Chao (Department of General Surgery, Huashan Hospital, Fudan University) ;
  • Zhao, Jing (Department of Infectious Diseases, Huashan Hospital, Fudan University) ;
  • Hu, Cheng-En (Department of General Surgery, Huashan Hospital, Fudan University) ;
  • Gan, Jun (Department of General Surgery, Huashan Hospital, Fudan University) ;
  • Zhang, Wen-Hong (Department of Infectious Diseases, Huashan Hospital, Fudan University) ;
  • Huang, Guang-Jian (Department of General Surgery, Huashan Hospital, Fudan University)
  • Published : 2014.03.01

Abstract

Background: Vascular endothelial growth factor-C (VEGF-C), which contributes to lymphatic metastasis (LM) in malignant disease, is one of the most important factors involved in physical and pathological lymphangiogenesis. Some VEGF-C related factors such as sine oculis homeobox homolog (SIX) 1, contactin (CNTN) 1 and dual specificity phosphatase (DUSP) 6 have been extensively studied in malignancies, but their expression levels and associations have still to be elucidated in stomach cancer. Methods: We detected their expression levels in 30 paired stomach cancer tissues using quantitative real-time reverse transcription-PCR (qRT-PCR). The expression and clinical significance of each factor was analyzed using Wilcoxon signed rank sum test. The correlation among all the factors was performed by Spearman rank correlation analysis. Results: The results suggest that VEGF-C and CNTN1 are significantly correlated with tumor size, SIX1 with the age and CNTN1 also with the cTNM stage. There are significant correlations of expression levels among VEGF-C, SIX1, CNTN1 and DUSP6. Conclusions: There exists an important regulatory crosstalk involving SIX1, VEGF-C, CNTN1 and DUSP6 in stomach cancer.

Keywords

References

  1. Achen MG, Stacker SA (2008). Molecular control of lymphatic metastasis. Ann N Y Acad Sci, 1131, 225-34. https://doi.org/10.1196/annals.1413.020
  2. Alitalo K, Carmeliet P (2002). Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell, 1, 219-27. https://doi.org/10.1016/S1535-6108(02)00051-X
  3. Amioka T, Kitadai Y, Tanaka S, et al (2002). Vascular endothelial growth factor-C expression predicts lymph node metastasis of human gastric carcinomas invading the submucosa. Eur J Cancer, 38, 1413-9. https://doi.org/10.1016/S0959-8049(02)00106-5
  4. Arigami T, Natsugoe S, Uenosono Y, et al (2009). Vascular endothelial growth factor-C and -D expression correlates with lymph node micrometastasis in pN0 early gastric cancer. J Surg Oncol, 99, 148-53. https://doi.org/10.1002/jso.21228
  5. Cao Y (2008). Why and how do tumors stimulate lymphangiogenesis? Lymphat Res Biol, 6, 145-8. https://doi.org/10.1089/lrb.2008.1007
  6. Cejudo-Marin R, Tarrega C, Nunes-Xavier CE, Pulido R (2012). Caspase-3 cleavage of DUSP6/MKP3 at the interdomain region generates active MKP3 fragments that regulate ERK1/2 subcellular localization and function. J Mol Biol, 420, 128-38. https://doi.org/10.1016/j.jmb.2012.04.004
  7. Christensen KL, Patrick AN, McCoy EL, Ford HL (2008). The six family of homeobox genes in development and cancer. Adv Cancer Res, 101, 93-126. https://doi.org/10.1016/S0065-230X(08)00405-3
  8. Furukawa T, Tanji E, Xu S, Horii A (2008). Feedback regulation of DUSP6 transcription responding to MAPK1 via ETS2 in human cells. Biochem Biophys Res Commun, 377, 317-20. https://doi.org/10.1016/j.bbrc.2008.10.003
  9. Guggenheim DE, Shah MA (2012). Gastric cancer epidemiology and risk factors. J Surg Oncol, 107, 230-6.
  10. Jennbacken K, Vallbo C, Wang W, Damber JE (2005). Expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 in human prostate cancer is associated with regional lymph node metastasis. Prostate, 65, 110-6. https://doi.org/10.1002/pros.20276
  11. Joukov V, Pajusola K, Kaipainen A, et al (1996). A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J, 15, 290-98.
  12. Joukov V, Sorsa T, Kumar V, et al (1997). Proteolytic processing regulates receptor specificity and activity of VEGF-C. EMBO J, 16, 3898-911. https://doi.org/10.1093/emboj/16.13.3898
  13. Kodama M, Kitadai Y, Tanaka M, et al (2008). Vascular endothelial growth factor C stimulates progression of human gastric cancer via both autocrine and paracrine mechanisms. Clin Cancer Res, 14, 7205-14. https://doi.org/10.1158/1078-0432.CCR-08-0818
  14. Kumar JP (2009). The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease. Cell Mol Life Sci, 66, 565-83. https://doi.org/10.1007/s00018-008-8335-4
  15. Le Grand F, Grifone R, Mourikis P, et al (2012). Six1 regulates stem cell repair potential and self-renewal during skeletal muscle regeneration. J Cell Biol, 198, 815-32. https://doi.org/10.1083/jcb.201201050
  16. Liu P, Zhou J, Zhu H, et al (2011). VEGF-C promotes the development of esophageal cancer via regulating CNTN-1 expression. Cytokine, 55, 8-17. https://doi.org/10.1016/j.cyto.2011.03.008
  17. Liu Y, Zhang C, Fan J, et al (2011). Comprehensive analysis of clinical significance of stem-cell related factors in renal cell cancer. World J Surg Oncol, 9, 121. https://doi.org/10.1186/1477-7819-9-121
  18. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) Method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  19. Maillet M, Purcell NH, Sargent MA, et al (2008). DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility. J Biol Chem, 283, 31246-55. https://doi.org/10.1074/jbc.M806085200
  20. Peng C, Sun Q, Fang Y, et al (2011). VEGF-C antisense oligoxydeonucleotide suppression of invasive ability of the A-549 lung carcinoma cell line. Asian Pac J Cancer Prev, 12, 2097-9.
  21. Su JL, Yang PC, Shih JY, et al (2006). The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells. Cancer Cell, 9, 209-23. https://doi.org/10.1016/j.ccr.2006.02.018
  22. Su JL, Yen CJ, Chen PS, et al (2007). The role of the VEGF-C/VEGFR-3 axis in cancer progression. Br J Cancer, 96, 541-5. https://doi.org/10.1038/sj.bjc.6603487
  23. Tsai PW, Shiah SG, Lin MT, et al (2003). Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-beta 1. A critical role of p38/nuclear factor-kappa B signaling pathway. J Biol Chem, 278, 5750-9. https://doi.org/10.1074/jbc.M204863200
  24. Wang CA, Jedlicka P, Patrick AN, et al (2012). SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer. J Clin Invest, 122, 1895-906. https://doi.org/10.1172/JCI59858
  25. Wang J, Guo Y, Wang B, et al (2012). Lymphatic microvessel density and vascular endothelial growth factor-C and -D as prognostic factors in breast cancer: a systematic review and meta-analysis of the literature. Mol Biol Rep, 39, 11153-65. https://doi.org/10.1007/s11033-012-2024-y
  26. Wang Z, Chen Y, Li X, et al (2012). Expression of VEGF-C/VEGFR-3 in human laryngeal squamous cell carcinomas and its significance for lymphatic metastasis. Asian Pac J Cancer Prev, 13, 27-31. https://doi.org/10.7314/APJCP.2012.13.1.027
  27. Wu WK, Cho CH, Lee CW, et al (2010). Dysregulation of cellular signaling in gastric cancer. Cancer Lett, 295, 144-53. https://doi.org/10.1016/j.canlet.2010.04.025
  28. Zhu C, Qi X, Chen Y, et al (2011). PI3K/Akt and MAPK/ERK1/2 signaling pathways are involved in IGF-1-induced VEGF-C upregulation in breast cancer. J Cancer Res Clin Oncol, 137, 1587-94. https://doi.org/10.1007/s00432-011-1049-2

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