Lung Adenocarcinoma Originates from Retrovirus Infection of Proliferating Type 2 Pneumocytes during Pulmonary Post-Natal Development or Tissue Repair

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Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer.

Vyšlo v časopise: Lung Adenocarcinoma Originates from Retrovirus Infection of Proliferating Type 2 Pneumocytes during Pulmonary Post-Natal Development or Tissue Repair. PLoS Pathog 7(3): e32767. doi:10.1371/journal.ppat.1002014
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002014

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1. CoffinJMHughesSHVarmusHE 1997 Retroviruses New York Cold Spring Harbor Laboratory Press 843

2. BanerjeePCrawfordLSamuelsonEFeuerG 2010 Hematopoietic stem cells and retroviral infection. Retrovirology 7 8

3. ClarkeMFDickJEDirksPBEavesCJJamiesonCH 2006 Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66 9339 9344

4. ReyaTMorrisonSJClarkeMFWeissmanIL 2001 Stem cells, cancer, and cancer stem cells. Nature 414 105 111

5. HillRP 2006 Identifying cancer stem cells in solid tumors: case not proven. Cancer Res 66 1891 1895; discussion 1890

6. VisvaderJELindemanGJ 2008 Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8 755 768

7. ZhouBBZhangHDamelinMGelesKGGrindleyJC 2009 Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov 8 806 823

8. RosenbergNJolicoeurP 1997 Retroviral pathogenesis. CoffinJMHughesSVarmusHE Retroviruses New York Cold Spring Harbor laboratory Press 475585

9. FanH 2003 Jaagsiekte sheep retrovirus and lung cancer Berlin Springer-Verlag

10. PalmariniM 2007 A veterinary twist on pathogen biology. PLoS Pathog 3 e12

11. PalmariniMSharpJMDe las HerasMFanH 1999 Jaagsiekte sheep retrovirus is necessary and sufficient to induce a contagious lung cancer in sheep. J Virol 73 6964 6972

12. PalmariniMFanH 2001 Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer. J Natl Cancer Inst 93 1603 1614

13. LiuSLMillerAD 2007 Oncogenic transformation by the jaagsiekte sheep retrovirus envelope protein. Oncogene 26 789 801

14. AllenTESherrillKJCrispellSMPerrottMRCarlsonJO 2002 The jaagsiekte sheep retrovirus envelope gene induces transformation of the avian fibroblast cell line DF-1 but does not require a conserved SH2 binding domain. J Gen Virol 83 2733 2742

15. MaedaNPalmariniMMurgiaCFanH 2001 Direct transformation of rodent fibroblasts by jaagsiekte sheep retrovirus DNA. Proc Natl Acad Sci U S A 98 4449 4454

16. RaiSKDuhFMVigdorovichVDanilkovitch-MiagkovaALermanMI 2001 Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. Proc Natl Acad Sci U S A 98 4443 4448

17. LiuSLDuhFMLermanMIMillerAD 2003 Role of virus receptor Hyal2 in oncogenic transformation of rodent fibroblasts by sheep betaretrovirus env proteins. J Virol 77 2850 2858

18. LiuSLMillerAD 2005 Transformation of madin-darby canine kidney epithelial cells by sheep retrovirus envelope proteins. J Virol 79 927 933

19. MaedaNInoshimaYFrumanDABrachmannSMFanH 2003 Transformation of mouse fibrobalsts by jaagsiekte sheep retrovirus envelope does not require phosphatidylinositol 3-kinase. J Virol 77 9951 9959

20. PalmariniMMaedaNMurgiaCDe-FrajaCHofacreA 2001 A phosphatidylinositol 3-kinase docking site in the cytoplasmic tail of the Jaagsiekte sheep retrovirus transmembrane protein is essential for envelope-induced transformation of NIH 3T3 cells. J Virol 75 11002 11009

21. ZavalaGPrettoCChowYHJonesLAlbertiA 2003 Relevance of Akt phosphorylation in cell transformation induced by Jaagsiekte sheep retrovirus. Virology 312 95 105

22. JohnsonCSandersKFanH 2010 Jaagsiekte sheep retrovirus transformation in Madin-Darby canine kidney epithelial cell three-dimensional culture. J Virol 84 5379 5390

23. CaporaleMCousensCCentoramePPinoniCDe las HerasM 2006 Expression of the Jaagsiekte sheep retrovirus envelope glycoproteins is sufficient to induce lung tumor in sheep. J Virol 80 8030 8037

24. WoottonSKHalbertCLMillerAD 2005 Sheep retrovirus structural protein induces lung tumours. Nature 434 904 907

25. MaedaNFuWOrtinAde las HerasMFanH 2005 Roles of the Ras-MEK-mitogen-activated protein kinase and phosphatidylinositol 3-kinase-Akt-mTOR pathways in Jaagsiekte sheep retrovirus-induced transformation of rodent fibroblast and epithelial cell lines. J Virol 79 4440 4450

26. LiuSLLermanMIMillerAD 2003 Putative phosphatidylinositol 3-kinase (PI3K) binding motifs in ovine betaretrovirus Env proteins are not essential for rodent fibroblast transformation and PI3K/Akt activation. J Virol 77 7924 7935

27. De Las HerasMOrtinABenitoASummersCFerrerLM 2006 In-situ demonstration of mitogen-activated protein kinase Erk 1/2 signalling pathway in contagious respiratory tumours of sheep and goats. J Comp Pathol 135 1 10

28. SharpJMAngusKWGrayEWScottFM 1983 Rapid transmission of sheep pulmonary adenomatosis (jaagsiekte) in young lambs. Brief report. Arch Virol 78 89 95

29. SalvatoriDGonzalezLDewarPCousensCde las HerasM 2004 Successful induction of ovine pulmonary adenocarcinoma in lambs of different ages and detection of viraemia during the preclinical period. J Gen Virol 85 3319 3324

30. HollandMJPalmariniMGarcia-GotiMGonzalezLMcKendrickI 1999 Jaagsiekte retrovirus is widely distributed both in T and B lymphocytes and in mononuclear phagocytes of sheep with naturally and experimentally acquired pulmonary adenomatosis. J Virol 73 4004 4008

31. PalmariniMHollandMJCousensCDalzielRGSharpJM 1996 Jaagsiekte retrovirus establishes a disseminated infection of the lymphoid tissues of sheep affected by pulmonary adenomatosis. J Gen Virol 77 2991 2998

32. PalmariniMSharpJMLeeCFanH 1999 In vitro infection of ovine cell lines by jaagsiekte sheep retrovirus (JSRV). J Virol 73 10070 10078

33. RaiSKDeMartiniJCMillerAD 2000 Retrovirus vectors bearing jaagsiekte sheep retrovirus Env transduce human cells by using a new receptor localized to chromosome 3p21.3. J Virol 74 4698 4704

34. ArnaudFCaporaleMVarelaMBiekRChessaB 2007 A paradigm for virus-host coevolution: sequential counter-adaptations between endogenous and exogenous retroviruses. PLoS Pathog 3 e170

35. ArnaudFVarelaMSpencerTEPalmariniM 2008 Coevolution of endogenous Betaretroviruses of sheep and their host. Cell Mol Life Sci 65 3422 3432

36. OrtinAMinguijonEDewarPGarciaMFerrerLM 1998 Lack of a specific immune response against a recombinant capsid protein of Jaagsiekte sheep retrovirus in sheep and goats naturally affected by enzootic nasal tumour or sheep pulmonary adenomatosis. Vet Immunol Immunopathol 61 229 237

37. ChessaBPereiraFArnaudFAmorimAGoyacheF 2009 Revealing the history of sheep domestication using retrovirus integrations. Science 324 532 536

38. PalmariniMDewarPDe las HerasMInglisNFDalzielRG 1995 Epithelial tumour cells in the lungs of sheep with pulmonary adenomatosis are major sites of replication for Jaagsiekte retrovirus. J Gen Virol 76 2731 2737

39. CaporaleMCentoramePGiovanniniASacchiniFDi VenturaM 2005 Infection of lung epithelial cells and induction of pulmonary adenocarcinoma is not the most common outcome of naturally occurring JSRV infection during the commercial lifespan of sheep. Virology 338 144 153

40. PlattJAKraipowichNVillafaneFDeMartiniJC 2002 Alveolar type II cells expressing jaagsiekte sheep retrovirus capsid protein and surfactant proteins are the predominant neoplastic cell type in ovine pulmonary adenocarcinoma. Vet Pathol 39 341 352

41. De las HerasMGonzalezLSharpJM 2003 Pathology of ovine pulmonary adenocarcinoma. Curr Top Microbiol Immunol 275 25 54

42. BeytutESozmenMErginsoyS 2009 Immunohistochemical detection of pulmonary surfactant proteins and retroviral antigens in the lungs of sheep with pulmonary adenomatosis. J Comp Pathol 140 43 53

43. KimCFJacksonELWoolfendenAELawrenceSBabarI 2005 Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121 823 835

44. RawlinsELOkuboTXueYBrassDMAutenRL 2009 The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 4 525 534

45. GiangrecoAArwertENRosewellIRSnyderJWattFM 2009 Stem cells are dispensable for lung homeostasis but restore airways after injury. Proc Natl Acad Sci U S A 106 9286 9291

46. CaporaleMArnaudFMuraMGolderMMurgiaC 2009 The signal peptide of a simple retrovirus envelope functions as a posttranscriptional regulator of viral gene expression. J Virol 83 4591 4604

47. QuadeK 1979 Transformation of mammalian cells by avian myelocytomatosis virus and avian erythroblastosis virus. Virology 98 461 465

48. PalmariniMCousensCDalzielRGBaiJStedmanK 1996 The exogenous form of Jaagsiekte retrovirus is specifically associated with a contagious lung cancer of sheep. J Virol 70 1618 1623

49. WoottonSKMetzgerMJHudkinsKLAlpersCEYorkD 2006 Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV. Retrovirology 3 94

50. DonelloJELoebJEHopeTJ 1998 Woodchuck hepatitis virus contains a tripartite posttranscriptional regulatory element. J Virol 72 5085 5092

51. SchwenterFDeglonNAebischerP 2003 Optimization of human erythropoietin secretion from MLV-infected human primary fibroblasts used for encapsulated cell therapy. J Gene Med 5 246 257

52. BrayMPrasadSDubayJWHunterEJeangKT 1994 A small element from the Mason-Pfizer monkey virus genome makes human immunodeficiency virus type 1 expression and replication Rev-independent. Proc Natl Acad Sci U S A 91 1256 1260

53. ZolotukhinASValentinAPavlakisGNFelberBK 1994 Continuous propagation of RRE(-) and Rev(-)RRE(-) human immunodeficiency virus type 1 molecular clones containing a cis-acting element of simian retrovirus type 1 in human peripheral blood lymphocytes. J Virol 68 7944 7952

54. MillerADChenF 1996 Retrovirus packaging cells based on 10A1 murine leukemia virus for production of vectors that use multiple receptors for cell entry. J Virol 70 5564 5571

55. ZaffranSAstierMGratecosDSemerivaM 1997 The held out wings (how) Drosophila gene encodes a putative RNA-binding protein involved in the control of muscular and cardiac activity. Development 124 2087 2098

56. NaldiniLBlomerUGallayPOryDMulliganR 1996 In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272 263 267

57. BahnsonABDuniganJTBaysalBEMohneyTAtchisonRW 1995 Centrifugal enhancement of retroviral mediated gene transfer. J Virol Methods 54 131 143

58. O'DohertyUSwiggardWJMalimMH 2000 Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol 74 10074 10080

59. DeMartiniJCRosadioRHSharpJMRussellHILairmoreMD 1987 Experimental coinduction of type D retrovirus-associated pulmonary carcinoma and lentivirus-associated lymphoid interstitial pneumonia in lambs. J Natl Cancer Inst 79 167 177

60. NisbetDIMackayJMSmithWGrayEW 1971 Ultrastructure of sheep pulmonary adenomatosis (Jaagsiekte). J Pathol 103 157 162

61. PayneALVerwoerdDW 1984 A scanning and transmission electron microscopy study of jaagsiekte lesions. Onderstepoort J Vet Res 51 1 13

62. PerkKHodINobelTA 1971 Pulmonary adenomatosis of sheep (jaagsiekte). I. Ultrastructure of the tumor. J Natl Cancer Inst 46 525 537

63. PlopperCGHydeDMBuckpittAR 1997 Clara cells. CrystalRGWestJBWeibelERBarnesPJ The Lung: Scientific Foundations Philadelphia Lippincott-Raven 517 533

64. WhitsettJAGlasserSW 1998 Regulation of surfactant protein gene transcription. Biochim Biophys Acta 1408 303 311

65. VerwoerdDWWilliamsonALDe VilliersEM 1980 Aetiology of jaagsiekte: transmission by means of subcellular fractions and evidence for the involvement of a retrovirus. Onderstepoort J Vet Res 47 275 280

66. KauffmanSL 1980 Cell proliferation in the mammalian lung. Int Rev Exp Pathol 22 131 191

67. ZeltnerTBBurriPH 1987 The postnatal development and growth of the human lung. II. Morphology. Respir Physiol 67 269 282

68. ZeltnerTBCaduffJHGehrPPfenningerJBurriPH 1987 The postnatal development and growth of the human lung. I. Morphometry. Respir Physiol 67 247 267

69. KubbutatMHKeyGDuchrowMSchluterCFladHD 1994 Epitope analysis of antibodies recognising the cell proliferation associated nuclear antigen previously defined by the antibody Ki-67 (Ki-67 protein). J Clin Pathol 47 524 528

70. BradleyBJCarlsonJRDickinsonEO 1978 3-methylindole-induced pulmonary edema and emphysema in sheep. Am J Vet Res 39 1355 1358

71. LewisPFEmermanM 1994 Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol 68 510 516

72. MillerDGAdamMAMillerAD 1990 Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 10 4239 4242

73. RoeTReynoldsTCYuGBrownPO 1993 Integration of murine leukemia virus DNA depends on mitosis. Embo J 12 2099 2108

74. Rosai JaSLH 1995 Conditional Clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells Atlas of Tumor Pathology Washington DC Armed Forces Institute of Pathology

75. RawlinsELOkuboTQueJXueYClarkC 2008 Epithelial stem/progenitor cells in lung postnatal growth, maintenance, and repair. Cold Spring Harb Symp Quant Biol 73 291 295

76. ScheerlinckJPSnibsonKJBowlesVMSuttonP 2008 Biomedical applications of sheep models: from asthma to vaccines. Trends Biotechnol 26 259 266

77. HarrisA 1997 Towards an ovine model of cystic fibrosis. Hum Mol Genet 6 2191 2194

78. SharpJMDeMartiniJC 2003 Natural history of JSRV in sheep. Curr Top Microbiol Immunol 275 55 79

79. CousensCThonurLImlachSCrawfordJSalesJ 2009 Jaagsiekte sheep retrovirus is present at high concentration in lung fluid produced by ovine pulmonary adenocarcinoma-affected sheep and can survive for several weeks at ambient temperatures. Res Vet Sci 87 154 156

80. McGee-EstradaKFanH 2006 In Vivo and In Vitro Analysis of Factor Binding Sites in Jaagsiekte Sheep Retrovirus Long Terminal Repeat Enhancer Sequences: Roles of HNF-3, NF-I, and C/EBP for Activity in Lung Epithelial Cells. J Virol 80 332 341

81. McGee-EstradaKPalmariniMFanH 2002 HNF-3ß is a critical factor for the expression of the Jaagsiekte sheep retrovirus (JSRV) long terminal repeat in type II pneumocytes but not in clara cells. Virology 292 87 97

82. McGee-EstradaKPalmariniMHallwirthCFanH 2005 A Moloney murine leukemia virus driven by the Jaagsiekte sheep retrovirus enhancers shows enhanced specificity for infectivity in lung epithelial cells. Virus Genes 31 257 263

83. PalmariniMDattaSOmidRMurgiaCFanH 2000 The long terminal repeats of Jaagsiekte sheep retrovirus (JSRV) are preferentially active in type II pneumocytes. J Virol 74 5776 5787

84. DakessianRMFanH 2008 Specific in vivo expression in type II pneumocytes of the Jaagsiekte sheep retrovirus long terminal repeat in transgenic mice. Virology 372 398 408

85. WinkelmannANoackT 2010 The Clara cell: a “Third Reich eponym”? Eur Respir J 36 722 727