Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Neurotrophic Artemin Promotes Motility and Invasiveness of MIA PaCa-2 Pancreatic Cancer Cells

  • Meng, Ling-Xin (Department of Oncology, Affiliated Rizhao People's Hospital, Jining Medical University) ;
  • Chi, Yu-Hua (Department of Oncology, Affiliated Rizhao People's Hospital, Jining Medical University) ;
  • Wang, Xiang-Xu (Department of Oncology, Affiliated Rizhao People's Hospital, Jining Medical University) ;
  • Ding, Zhao-Jun (Department of Oncology, Affiliated Rizhao People's Hospital, Jining Medical University) ;
  • Fei, Li-Cong (Department of Oncology, Affiliated Rizhao People's Hospital, Jining Medical University) ;
  • Zhang, Hong (Department of Oncology, Affiliated Rizhao People's Hospital, Jining Medical University) ;
  • Mou, Ling (Department of Oncology, Affiliated Rizhao People's Hospital, Jining Medical University) ;
  • Cui, Wen (Department of Oncology, Affiliated Rizhao People's Hospital, Jining Medical University) ;
  • Xue, Ying-Jie (Department of Oncology, Affiliated Rizhao People's Hospital, Jining Medical University)
  • Published : 2012.05.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: To analyze the capacity of neurotrophic artemin to promote the motility and invasiveness of MIA PaCa-2 pancreatic cancer cells. Methods: MIA PaCa-2 was cultured in vitro and studied using transwell chambers for motility and invasiveness on treatment with different concentrations of aArtemin or its receptor $GFR{\alpha}3$ were also determined. Expression of matrix metalloproteinase-2 (MMP-2) and epithelial cadherin (E-cadherin) was quantified using RT-PCR and Western blotting. Results: MIA PaCa-2 pancreatic cancer cell motility and invasiveness was significantly increased with artemin and its receptor $GFR{\alpha}3$ with dose dependence (P<0.01). MMP-2 production was also significantly increased (t = 6.35, t = 7.32), while E-cadherin was significantly lowered (t = 4.27, t = 5.61) (P <0.01). Conclusion: Artemin and its receptor $GFR{\alpha}3$ can promote pancreatic cancer cell motility and invasiveness and contribute to aggressive behavior. The mechanism may be related to increased expression of MMP-2 molecule and down-regulation of E-cadherin expression.

Keywords

References

  1. Airaksinen MS, Holm L, Hatinen T (2006). Evolution of the GDNF family ligands and receptors. Brain Behav Evol, 68, 181-90. https://doi.org/10.1159/000094087
  2. Andres R, Forgie A, Wyatt S, et al (2001). Multiple effects of artemin on sympathetic neurone generation, survival and growth. Development, 128, 3685-95.
  3. Baloh RH, Tansey MG, Johnson EM Jr, Milbrandt J (2000). Functional mapping of receptor specificity domains of glial cell line-derived neurotrophic factor (GDNF) family ligands and production of GFRalpha1 RET-specific agonists. J Biol Chem, 275, 3412-20. https://doi.org/10.1074/jbc.275.5.3412
  4. Baloh RH, Tansey MG, Lampe PA, et al (1998). Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex. Neuron, 21, 1291-302. https://doi.org/10.1016/S0896-6273(00)80649-2
  5. Ceyhan GO, Giese NA, Erkan M, et al (2006). The neurotrophic factor artemin promotes pancreatic cancer invasion. Ann Surg, 244, 274-81. https://doi.org/10.1097/01.sla.0000217642.68697.55
  6. Enomoto H, Crawford PA, Gorodinsky A, et al (2001). RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons. Development, 128, 3963-74.
  7. Honma Y, Araki T, Gianino S, et al (2002). Artemin is a vascularderived neurotropic factor for developing sympathetic neurons. Neuron, 35, 267-82. https://doi.org/10.1016/S0896-6273(02)00774-2
  8. Jemal A, Siegel R, Ward E, et al (2009). Cancer statistics, 2009. CA Cancer J Clin, 59, 225-49. https://doi.org/10.3322/caac.20006
  9. Jo Chae K, Rha SY, Oh BK, et al (2004). Expression of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 and -2 in intraductal and nonintraductal growth type of cholangiocarcinoma. Am J Gastroenterol, 99, 68-75. https://doi.org/10.1046/j.1572-0241.2003.04025.x
  10. Kao WT, Lin CY, Lee LT, et al (2008). Investigation of MMP-2 and -9 in a highly invasive A431 tumor cell sub-line selected from a Boyden chamber assay. Anticancer Res, 28, 2109-20.
  11. Li S, Li Z, Guo F, et al (2011). miR-223 regulates migration and invasion by targeting Artemin in human esophageal carcinoma. J Biomed Sci, 18, 24. https://doi.org/10.1186/1423-0127-18-24
  12. Lomberk G (2008). Pain management. Pancreatology, 8, 542-3. https://doi.org/10.1159/000159211
  13. McLaughlin RB, Montone KT, Wall SJ, et al (1999). Nerve cell adhesion molecule expression in squamous cell carcinoma of the head and neck: a predictor of propensity toward perineural spread. Laryngoscope, 109, 821-6. https://doi.org/10.1097/00005537-199905000-00026
  14. Meng LX, LI Q, Xue YJ, et al (2008). Effects of nerve growth factor on invasive ability of human pancreatic cancer cell line MIA PaCa-2. Chin J Hepatobiliary Surg (Chinese), 14, 796-800.
  15. Okada Y, Takeyama H, Sato M, et al (1999). Experimental implication of celiac ganglionotropic invasion of pancreaticcancer cells bearing c-ret protooncogene with reference to glial-cell-line-derived neurotrophic factor (GDNF). Int J Cance, 81, 67-73. https://doi.org/10.1002/(SICI)1097-0215(19990331)81:1<67::AID-IJC13>3.0.CO;2-V
  16. Orozco OE, Walus L, Sah DW, Pepinsky RB, Sanicola M (2001). GFRalpha3 is expressed predominantly in nociceptive sensory neurons. Eur J Neurosci, 13, 2177-82. https://doi.org/10.1046/j.0953-816x.2001.01596.x
  17. Ruckert F, Gorgens H, Richter I, et al (2011). RET-protooncogene variants in patients with sporadic neoplasms of the digestive tract and the central nervous system. Int J Colorectal Dis, 26, 835-40. https://doi.org/10.1007/s00384-011-1150-7
  18. Takahashi M (2001). The GDNF/RET signaling pathway and human diseases. Cytokine Growth Factor Rev, 12, 361-73. https://doi.org/10.1016/S1359-6101(01)00012-0
  19. Terada T, Okada Y, Nakanuma Y (1995). Expression of matrix proteinases during human intrahepatic bile duct development. A possible role in biliary cell migration. Am J Pathol, 147, 1207-13.
  20. Torer N, Kayaselcuk F, Nursal TZ, et al (2007). Adhesion molecules as prognostic markers in pancreatic adenocarcinoma. J Surg Oncol, 96, 419-23. https://doi.org/10.1002/jso.20654
  21. Veit C, Genze F, Menke A, et al (2004). Activation of phosphatidylinositol 3-kinase and extracellular signalregulated kinase is required for glial cell line-derived neurotrophic factor-induced migration and invasion of pancreatic carcinoma cells. Cancer Res, 64, 5291-300. https://doi.org/10.1158/0008-5472.CAN-04-1112
  22. von Burstin J, Eser S, Paul MC, et al (2009). E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex. Gastroenterology, 137, 361-71. https://doi.org/10.1053/j.gastro.2009.04.004
  23. Winter JM, Ting AH, Vilardell F, et al (2008). Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin Cancer Res, 14, 412-8. https://doi.org/10.1158/1078-0432.CCR-07-0487

Cited by

  1. GFRA3 promoter methylation may be associated with decreased postoperative survival in gastric cancer vol.16, pp.1, 2016, https://doi.org/10.1186/s12885-016-2247-8
  2. Systemic Depletion of Nerve Growth Factor Inhibits Disease Progression in a Genetically Engineered Model of Pancreatic Ductal Adenocarcinoma vol.47, pp.7, 2018, https://doi.org/10.1097/MPA.0000000000001090
  3. Role of artemin in non-small cell lung cancer vol.9, pp.5, 2018, https://doi.org/10.1111/1759-7714.12615