Axon guidance factor SLIT2 inhibits neural invasion and metastasis in pancreatic cancer

Cancer Research

Volumn 74, Issue 5, 2014, Pages 1529-1540

  Gohrig, Andreas ^a,b   Detjen, Katharina M ^a,b   Hilfenhaus, Georg ^b   Korner, Jan L ^b   Welzel, Martina ^a,b   Arsenic, Ruza ^b   Schmuck, Rosa ^c   Bahra, Marcus ^c   Wu, Jane Y ^d   Wiedenmann, Bertram ^b   Fischer, Christian ^a,b  

^a MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c Klinik fur Viszeral Allgemein und Transplantationschirurgie   (Germany)

^d NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; ROUNDABOUT RECEPTOR; SLIT2 PROTEIN;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL CULTURE; CANCER INCIDENCE; CANCER TISSUE; CELL MOTILITY; CONTROLLED STUDY; DOWN REGULATION; FEMALE; GENE EXPRESSION REGULATION; GENE SILENCING; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; INHIBITION KINETICS; LYMPH NODE METASTASIS; MOUSE; NONHUMAN; PANCREAS ADENOCARCINOMA; PRIORITY JOURNAL; RNA INTERFERENCE; ROBO1 GENE; SIGNAL TRANSDUCTION; SLIT2 GENE; TUMOR ESCAPE; TUMOR INVASION; TUMOR VASCULARIZATION; UMBILICAL VEIN ENDOTHELIAL CELL;

AXONS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE; CELL LINE, TUMOR; CELL MOVEMENT; CHEMOTAXIS; ENDOTHELIAL CELLS; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LYMPHATIC METASTASIS; NERVE TISSUE PROTEINS; NEURONS; PANCREATIC NEOPLASMS; RECEPTORS, IMMUNOLOGIC; SIGNAL TRANSDUCTION;

EID: 84896537459     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-13-1012     Document Type: Article

References (50)

1. Stathis A, Moore MJ. Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev 2010;7:163-72.
2. Bapat AA, Hostetter G, Von Hoff DD, Han H. Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer 2011;11: 695-707.
3. Gil Z, Cavel O, Kelly K, Brader P, Rein A, Gao SP, et al. Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves. J Natl Cancer Inst 2010;102:107-18.
4. Ceyhan GO, Demir IE, Altintas B, Rauch U, Thiel G, M̈uller MW, et al. Neural invasion in pancreatic cancer: a mutual tropism between neurons and cancer cells. Biochem Biophys Res Commun 2008; 374:442-7.
5. Ceyhan GO, Bergmann F, Kadihasanoglu M, Altintas B, Demir IE, Hinz U, et al. Pancreatic neuropathy and neuropathic pain-A comprehensive pathomorphological study of 546 cases. Gastroenterology 2009;136:177-86e1.
6. Tessier-Lavigne M, Goodman CS. The molecular biology of axon guidance. Science 1996;274:1123-33.
7. Carmeliet P, Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature 2005;436:193-200.
8. Chedotal A. Slits and their receptors. Adv Exp Med Biol 2007;621: 65-80.
9. Mehlen P, Delloye-Bourgeois C, Chedotal A. Novel roles for Slits and netrins: axon guidance cues as anticancer targets? Nat Rev Cancer 2011;11:188-97.
10. Ballard MS, Hinck L. A roundabout way to cancer. Adv Cancer Res 2012;114:187-235.
11. Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, et al. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 1999;96:795-806.
12. Ypsilanti AR, Zagar Y, Chedotal A. Moving away from the midline: new developments for Slit and Robo. Development 2010;137: 1939-52.
13. Li HS, Chen JH,WuW, Fagaly T, Zhou L, Yuan W, et al. Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons. Cell 1999;96:807-18.
14. Yuasa-Kawada J, Kinoshita-Kawada M, Wu G, Rao Y, Wu JY. Midline crossing and Slit responsiveness of commissural axons require USP33. Nat Neurosci 2009;12:1087-9.
15. Wu W, Wong K, Chen J, Jiang Z, Dupuis S, Wu JY, et al. Directional guidance of neuronal migration in the olfactory system by the protein Slit. Nature 1999;400:331-6.
16. Jia L, Cheng L, Raper J. Slit/Robo signaling is necessary to confine early neural crest cells to the ventral migratory pathway in the trunk. Dev Biol 2005;282:411-21.
17. Giovannone D, Reyes M, Reyes R, Correa L, Martinez D, Ra H, et al. Slits affect the timely migration of neural crest cells via Robo receptor. Dev Dyn 2012;241:1274-88.
18. Bedell VM, Yeo SY, Park KW, Chung J, Seth P, Shivalingappa V, et al. roundabout4 is essential for angiogenesis in vivo. Proc Natl Acad Sci U S A 2005;102:6373-8.
19. Park KW, Morrison CM, Sorensen LK, Jones CA, Rao Y, Chien CB, et al. Robo4 is a vascular-specific receptor that inhibits endothelial migration. Dev Biol 2003;261:251-67.
20. Grieshammer U, Le M, Plump AS, Wang F, Tessier-Lavigne M, Martin GR. SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev Cell 2004;6:709-17.
21. Macias H, Moran A, Samara Y, Moreno M, Compton JE, Harburg G, et al. SLIT/ROBO1 signaling suppresses mammary branching morphogenesis by limiting basal cell number. Dev Cell 2011;20:827-40.
22. Xian J, Clark KJ, Fordham R, Pannell R, Rabbitts TH, Rabbitts PH. Inadequate lung development and bronchial hyperplasia in mice with a targeted deletion in the Dutt1/Robo1 gene. Proc Natl Acad Sci U S A 2001;98:15062-6.
23. Wang B, Xiao Y, Ding BB, Zhang N, Yuan X, Gui L, et al. Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. Cancer Cell 2003;4:19-29.
24. Dallol A, Da Silva NF, Viacava P, Minna JD, Bieche I, Maher ER, et al. SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers. Cancer Res 2002;62:5874-80.
25. Dallol A, Morton D, Maher ER, Latif F. SLIT2 axon guidance molecule is frequently inactivated in colorectal cancer and suppresses growth of colorectal carcinoma cells. Cancer Res 2003;63:1054-8.
26. Schulz P, Fischer C, Detjen KM, Rieke S, Hilfenhaus G, von Marschall Z, et al. Angiopoietin-2 drives lymphatic metastasis of pancreatic cancer. Faseb J 2011;25:3325-35.
27. Furukawa T, Duguid WP, Rosenberg L, Viallet J, Galloway DA, Tsao MS. Long-Term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16. Am J Pathol 1996;148:1763-70.
28. Ouyang H, Mou L, Luk C, Liu N, Karaskova J, Squire J, et al. Immortal human pancreatic duct epithelial cell lines with near normal genotype and phenotype. Am J Pathol 2000;157:1623-31.
29. Fischer C, Jonckx B, Mazzone M, Zacchigna S, Loges S, Pattarini L, et al. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 2007;131:463-75.
30. Schulz P, Scholz A, Rexin A, Hauff P, Schirner M, Wiedenmann B, et al. Inducible re-expression of p16 in an orthotopic mouse model of pancreatic cancer inhibits lymphangiogenesis and lymphatic metastasis. Br J Cancer 2008;99:110-7.
31. Hilfenhaus G, G̈ohrig A, Pape UF, Neumann T, Jann H, Zdunek D, et al. Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients. Endocr Relat Cancer 2013;20: 305-19.
32. Nguyen Ba-Charvet KT, Brose K, Ma L, Wang KH, Marillat V, Sotelo C, et al. Diversity and specificity of actions of Slit2 proteolytic fragments in axon guidance. J Neurosci 2001;21:4281-9.
33. Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012;491:399-405.
34. Tan AC, Jimeno A, Lin SH, Wheelhouse J, Chan F, Solomon A, et al. Characterizing DNA methylation patterns in pancreatic cancer genome. Mol Oncol 2009;3:425-38.
35. Vincent A, Omura N, Hong SM, Jaffe A, Eshleman J, Goggins M. Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma. Clin Cancer Res 2011;17:4341-54.
36. Stella MC, Trusolino L, Comoglio PM. The Slit/Robo system suppresses hepatocyte growth factor-dependent invasion and morphogenesis. Mol Biol Cell 2009;20:642-57.
37. Marlow R, Strickland P, Lee JS, Wu X, Pebenito M, Binnewies M, et al. SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium. Cancer Res 2008;68:7819-27.
38. Yuasa-Kawada J, Kinoshita-Kawada M, Rao Y, Wu JY. Deubiquitinating enzyme USP33/VDU1 is required for Slit signaling in inhibiting breast cancer cell migration. Proc Natl Acad Sci U S A 2009; 106:14530-5.
39. Chang PH, Hwang-Verslues WW, Chang YC, Chen CC, Hsiao M, Jeng YM, et al. Activation of Robo1 signaling of breast cancer cells by Slit2 from stromal fibroblast restrains tumorigenesis via blocking PI3K/Akt/ beta-catenin pathway. Cancer Res 2012;72:4652-61.
40. Tseng RC, Lee SH, Hsu HS, Chen BH, Tsai WC, Tzao C, et al. SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosis. Cancer Res 2010;70:543-51.
41. Kim HN, Choi DW, Lee KT, Lee JK, Heo JS, Choi SH, et al. Gene expression profiling in lymph node-positive and lymph node-negative pancreatic cancer. Pancreas 2007;34:325-34.
42. Nguyen-Ba-Charvet KT, Brose K, Marillat V, Sotelo C, Tessier-Lavigne M, Chedotal A. Sensory axon response to substrate-bound Slit2 is modulated by laminin and cyclic GMP. Mol Cell Neurosci 2001; 17:1048-58.
43. Dunaway CM, Hwang Y, Lindsley CW, Cook RS, Wu JY, Boothby M, et al. Cooperative signaling between Slit2 and Ephrin-A1 regulates a balance between angiogenesis and angiostasis. Mol Cell Biol 2011;31:404-16.
44. Marlow R, Binnewies M, Sorensen LK, Monica SD, Strickland P, Forsberg EC, et al. Vascular Robo4 restricts proangiogenic VEGF signaling in breast. Proc Natl Acad Sci U S A 2010;107:10520-5.
45. Jones CA, Nishiya N, London NR, Zhu W, Sorensen LK, Chan AC, et al. Slit2-Robo4 signalling promotes vascular stability by blocking Arf6 activity. Nat Cell Biol 2009;11:1325-31.
46. Jones CA, London NR, Chen H, Park KW, Sauvaget D, Stockton RA, et al. Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability. Nat Med 2008;14: 448-53.
47. Schmid BC, Rezniczek GA, Fabjani G, Yoneda T, Leodolter S, Zeillinger R. The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells. Breast Cancer Res Treat 2007;106:333-42.
48. Yang XM, Han HX, Sui F, Dai YM, Chen M, Geng JG. Slit-Robo signaling mediates lymphangiogenesis and promotes tumor lymphatic metastasis. Biochem Biophys Res Commun 2010;396: 571-7.
49. De Bellard ME, Rao Y, Bronner-Fraser M. Dual function of Slit2 in repulsion and enhanced migration of trunk, but not vagal, neural crest cells. J Cell Biol 2003;162:269-79.
50. Jaworski A, Tessier-Lavigne M. Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling. Nat Neurosci 2012;15: 367-9.