Epithelial-to-Mesenchymal Transition (EMT) in Intraductal Papillary Mucinous Neoplasm (IPMN) is Associated with High Tumor Grade and Adverse Outcomes

Annals of Surgical Oncology

Volumn 21, Issue 4, 2014, Pages 750-757

  Lahat, Guy ^a,b   Lubezky, Nir ^a,b   Loewenstein, Shelly ^a,b   Nizri, Eran ^a,b   Gan, Sarah ^a,b   Pasmanik Chor, Metzada ^b   Hayman, Luciile ^a,b   Barazowsky, Eli ^a,b   Ben Haim, Menahem ^a   Klausner, Joseph M ^a,b  

^a TEL AVIV SOURASKY MEDICAL CENTER   (Israel)

^b TEL AVIV UNIVERSITY   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

CADHERIN; HOMEODOMAIN PROTEIN; MICRORNA; TRANSCRIPTION FACTOR; TUMOR MARKER; VIMENTIN; ZEB1 PROTEIN, HUMAN;

ADENOCARCINOMA; AGED; CANCER GRADING; CELL TRANSFORMATION; CHEMISTRY; COLLOID CARCINOMA; DNA MICROARRAY; DOWN REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; FEMALE; GENE EXPRESSION PROFILING; GENETICS; HUMAN; LYMPH NODE METASTASIS; MALE; MIDDLE AGED; PANCREAS; PANCREAS CARCINOMA; PANCREAS TUMOR; PATHOLOGY; PROGNOSIS; SECONDARY; SURVIVAL RATE; UPREGULATION; VERY ELDERLY;

ADENOCARCINOMA, MUCINOUS; ADENOCARCINOMA, PAPILLARY; AGED; AGED, 80 AND OVER; CADHERINS; CARCINOMA, PANCREATIC DUCTAL; CELL TRANSFORMATION, NEOPLASTIC; DOWN-REGULATION; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; GENE EXPRESSION PROFILING; HOMEODOMAIN PROTEINS; HUMANS; LYMPHATIC METASTASIS; MALE; MICRORNAS; MIDDLE AGED; NEOPLASM GRADING; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PANCREAS; PANCREATIC NEOPLASMS; PROGNOSIS; SURVIVAL RATE; TRANSCRIPTION FACTORS; TUMOR MARKERS, BIOLOGICAL; UP-REGULATION; VIMENTIN;

EID: 84939891113     PISSN: 10689265     EISSN: 15344681     Source Type: Journal    
DOI: 10.1245/s10434-014-3946-5     Document Type: Article

References (49)

1. Savagner P. Leaving the neighborhood: molecular mechanisms involved during epithelial–mesenchymal transition. Bioessays. 2001;23:912–23.
2. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial–mesenchymal transitions in development and disease. Cell. 2009;139:871–90.
3. Berx G, Raspe E, Christofori G, Thiery JP, Sleeman JP. Pre-EMTing metastasis? Recapitulation of morphogenetic processes in cancer. Clin Exp Metastasis. 2007;24:587–97.
4. Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial–mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006;172:973–81.
5. Tarin D, Thompson EW, Newgreen DF. The fallacy of epithelial mesenchymal transition in neoplasia. Cancer Res. 2005;65:5996–6000.
6. Come C, Magnino F, Bibeau F, et al. Snail and slug play distinct roles during breast carcinoma progression. Clin Cancer Res. 2006;12:5395–402.
7. Saegusa M, Hashimura M, Kuwata T, Okayasu I. Requirement of the Akt/beta-catenin pathway for uterine carcinosarcoma genesis, modulating E-cadherin expression through the transactivation of slug. Am J Pathol. 2009;174:2107–15.
8. Yang J, Mani SA, Donaher JL, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.
9. Nieto MA. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol. 2002;3:155–66.
10. Wyatt L, Wadham C, Crocker LA, Lardelli M, Khew-Goodall Y. The protein tyrosine phosphatase Pez regulates TGFbeta, epithelial–mesenchymal transition, and organ development. J Cell Biol. 2007;178:1223–35.
11. Beach S, Tang H, Park S, et al. Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene. 2008;27:2243–8.
12. Weber JL, Kwitek AE, May PE, Wallace MR, Collins FS, Ledbetter DH. Dinucleotide repeat polymorphisms at the D17S250 and D17S261 loci. Nucleic Acids Res. 1990;18:4640.
13. Brabletz S, Brabletz T. The ZEB/miR-200 feedback loop—a motor of cellular plasticity in development and cancer? EMBO Rep. 2010;11:670–7.
14. Pan JJ, Yang MH. The role of epithelial–mesenchymal transition in pancreatic cancer. J Gastrointest Oncol. 2011;2:151–6.
15. Mongroo PS, Rustgi AK. The role of the miR-200 family in epithelial–mesenchymal transition. Cancer Biol Ther. 2010;10:219–22.
16. Mirzoeva OK, Collisson EA, Schaefer PM, et al. Subtype-specific MEK-PI3 kinase feedback as a therapeutic target in pancreatic adenocarcinoma. Mol Cancer Ther. 2013;12:2213–25.
17. Salvia R, Fernandez-del Castillo C, Bassi C, et al. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg. 2004;239:678–85.
18. Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg. 2004;239:788–97.
19. Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6:17–32.
20. Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12:183–97.
21. Tanno S, Nakano Y, Nishikawa T, et al. Natural history of branch duct intraductal papillary-mucinous neoplasms of the pancreas without mural nodules: long-term follow-up results. Gut. 2008;57:339–43.
22. Lee CJ, Scheiman J, Anderson MA, et al. Risk of malignancy in resected cystic tumors of the pancreas < or = 3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report. J Gastrointest Surg. 2008;12:234–42.
23. Rodriguez JR, Salvia R, Crippa S, et al. Branch-duct intraductal papillary mucinous neoplasms: observations in 145 patients who underwent resection. Gastroenterology. 2007;133:72–9.
24. Yamada S, Fuchs BC, Fujii T, et al. Epithelial-to-mesenchymal transition predicts prognosis of pancreatic cancer. Surgery. 2013;154:946–54.
25. Castellanos JA, Merchant NB, Nagathihalli NS. Emerging targets in pancreatic cancer: epithelial–mesenchymal transition and cancer stem cells. Onco Targets Ther. 2013;6:1261–7.
26. Su A, He S, Tian B, Hu W, Zhang Z. MicroRNA-221 mediates the effects of PDGF-BB on migration, proliferation, and the epithelial–mesenchymal transition in pancreatic cancer cells. PLoS One. 2013;8:e71309.
27. Rhim AD. Epithelial to mesenchymal transition and the generation of stem-like cells in pancreatic cancer. Pancreatology. 2013;13:114–7.
28. Hotz HG, Hotz B, Buhr HJ. Genes associated with epithelial–mesenchymal transition: possible therapeutic targets in ductal pancreatic adenocarcinoma? Anticancer Agents Med Chem. 2011;11:448–54.
29. Lahat G, Zhu QS, Huang KL, et al. Vimentin is a novel anti-cancer therapeutic target; insights from in vitro and in vivo mice xenograft studies. PLoS One. 2010;5:e10105.
30. Lubezky N, Loewenstein S, Ben-Haim M, et al. MicroRNA expression signatures in intraductal papillary mucinous neoplasm of the pancreas. Surgery. 2013;153:663–72.
31. Lopez-Novoa JM, Nieto MA. Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol Med. 2009;1:303–14.
32. Nakajima S, Doi R, Toyoda E, et al. N-cadherin expression and epithelial–mesenchymal transition in pancreatic carcinoma. Clin Cancer Res. 2004;10:4125–33.
33. Masugi Y, Yamazaki K, Hibi T, Aiura K, Kitagawa Y, Sakamoto M. Solitary cell infiltration is a novel indicator of poor prognosis and epithelial–mesenchymal transition in pancreatic cancer. Hum Pathol. 2010;41:1061–8.
34. Hotz B, Arndt M, Dullat S, Bhargava S, Buhr HJ, Hotz HG. Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer. Clin Cancer Res. 2007;13:4769–76.
35. Javle MM, Gibbs JF, Iwata KK, et al. Epithelial–mesenchymal transition (EMT) and activated extracellular signal–regulated kinase (p-Erk) in surgically resected pancreatic cancer. Ann Surg Oncol. 2007;14:3527–33.
36. Brabletz T. EMT and MET in metastasis: where are the cancer stem cells? Cancer Cell. 2012;22:699–701.
37. Gunasinghe NP, Wells A, Thompson EW, Hugo HJ. Mesenchymal–epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer. Cancer Metastasis Rev. 2012;31:469–78.
38. Aoyagi K, Tamaoki M, Nishumura T, Sasaki H. Technical considerations for analyzing EMT-MET data from surgical samples. Cancer Lett. 2013;341:105–10.
39. Krasnapolski MA, Todaro LB, de Kier Joffe EB. Is the epithelial-to-mesenchymal transition clinically relevant for the cancer patient? Curr Pharm Biotechnol. 2011;12:1891–9.
40. Chui MH. Insights into cancer metastasis from a clinicopathologic perspective: epithelial–mesenchymal transition is not a necessary step. Int J Cancer. 2013;132:1487–95.
41. Yamashita N, Tokunaga E, Kitao H, et al. Vimentin as a poor prognostic factor for triple-negative breast cancer. J Cancer Res Clin Oncol. 2013;139:739–46.
42. Yu J, Ren X, Chen Y, et al. Dysfunctional activation of neurotensin/IL-8 pathway in hepatocellular carcinoma is associated with increased inflammatory response in microenvironment, more epithelial mesenchymal transition in cancer and worse prognosis in patients. PLoS One. 2013;8:e56069.
43. Yokobori T, Iinuma H, Shimamura T, et al. Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial–mesenchymal transition and is associated with colorectal cancer prognosis. Cancer Res. 2013;73:2059–69.
44. Caries status in Europe and predictions of future trends. Caries Res. 1990;24:381–96.
45. Kabashima-Niibe A, Higuchi H, Takaishi H, et al. Mesenchymal stem cells regulate epithelial–mesenchymal transition and tumor progression of pancreatic cancer cells. Cancer Sci. 2013;104:157–64.
46. Arumugam T, Ramachandran V, Fournier KF, et al. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 2009;69:5820–8.
47. Pieraccioli M, Imbastari F, Antonov A, Melino G, Raschella G. Activation of miR200 by c-Myb depends on ZEB-1 expression and miR200 promoter methylation. Cell Cycle. 2013;12:2309–20.
48. Chu PY, Hu FW, Yu CC, et al. Epithelial–mesenchymal transition transcription factor ZEB-1/ZEB-2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer. Oral Oncol. 2013;49:34–41.
49. Wellner U, Schubert J, Burk UC, et al. The EMT-activator ZEB-1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 2009;11:1487–95.