Malignant Pleural Effusion

Chapter

Abstract

Malignant pleural effusion (MPE) poses a significant clinical problem annually affecting two million patients worldwide. MPE is most commonly caused by pleural metastasis of lung, breast, gastrointestinal, and other tumors, as opposed to the development of primary pleural-based malignancies, which are more infrequent. The appearance of a MPE in a patient with cancer signals systemic disease, short survival, and poor quality of life. Under normal conditions, the pleural space contains small amounts of fluid that are dynamically regulated by production via systemic blood vessel filtration and by lymphatic absorption. Any tumor-induced distortion of the pleural fluid production, circulation, and clearance process may result in MPE. Until recently, tumor-mediated obstruction of normal pleural fluid absorption was considered to be the most important path to MPE. However, recent advancements in experimental modeling of MPE indicate that tumor-induced inflammation, angiogenesis, and vascular hyperpermeability critically drive MPE formation independent from anatomical blockade of pleural fluid turnover. In this regard, different research groups have established novel experimental models mimicking human pleural malignancies, including models of human cancer induced-MPE in immunocompromized animals as well as mouse cancer-induced MPE in immunocompetent mice. These modeling approaches have expanded the field of pleural cancer research and will be addressed in detail in the present chapter.

Keywords

Vascular Endothelial Growth Factor Pleural Fluid Malignant Pleural Mesothelioma Pleural Cavity Lewis Lung Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Robinson BW, Lake RA (2005) Advances in malignant mesothelioma. N Engl J Med 353:1591–1603PubMedCrossRefGoogle Scholar
  2. 2.
    Scherpereel A, Astoul P, Baas P, Berghmans T, Clayson H, et al (2010) Guidelines of the european respiratory society and the european society of thoracic surgeons for the management of malignant pleural mesothelioma. Eur Respir J 35:479–495PubMedCrossRefGoogle Scholar
  3. 3.
    Lee YC, Light RW (2004) Management of malignant pleural effusions. Respirology 9:148–156PubMedCrossRefGoogle Scholar
  4. 4.
    Antony VB, Loddenkemper R, Astoul P, Boutin C, Goldstraw P, et al (2001) Management of malignant pleural effusions. Eur Respir J 18:402–419PubMedCrossRefGoogle Scholar
  5. 5.
    Henschke CI, Yankelevitz DF, Davis SD (1991) Pleural diseases: multimodality imaging and clinical management. Curr Probl Diagn Radiol 20:155–181.PubMedCrossRefGoogle Scholar
  6. 6.
    Noppen M, De Waele M, Li R, Gucht KV, D’Haese J, et al (2000) Volume and cellular content of normal pleural fluid in humans examined by pleural lavage. Am J Respir Crit Care Med 162:1023–1026PubMedCrossRefGoogle Scholar
  7. 7.
    Broaddus VC, Wiener-Kronish JP, Berthiaume Y, Staub NC (1988) Removal of pleural liquid and protein by lymphatics in awake sheep. J Appli Physiol 64:384–390Google Scholar
  8. 8.
    Agostoni E (1972) Mechanisms of the pleural space. Physiol Rev 52:57–128.PubMedGoogle Scholar
  9. 9.
    Zocchi L (2002) Physiology and pathophysiology of pleural fluid turnover. Eur Respir J 20:1545–1558PubMedCrossRefGoogle Scholar
  10. 10.
    Albertine KH, Wiener-Kronish JP, Bastacky J, Staub NC (1991) No evidence for mesothelial cell contact across the costal pleural space of sheep. J Appli Physiol 70:123–134Google Scholar
  11. 11.
    Albertine KH, Wiener-Kronish JP, Staub NC (1984) The structure of the parietal pleura and its relationship to pleural liquid dynamics in sheep. Anat Rec 208:401–409PubMedCrossRefGoogle Scholar
  12. 12.
    Albertine KH, Wiener-Kronish JP, Staub NC (1985) Blood supply of the caudal mediastinal lymph node in sheep. Anat Rec 212:129–131, 154–125CrossRefGoogle Scholar
  13. 13.
    Lai-Fook SJ (2004) Pleural mechanics and fluid exchange. Physiol Rev 84:385–410PubMedCrossRefGoogle Scholar
  14. 14.
    Miserocchi G (1997) Physiology and pathophysiology of pleural fluid turnover. Eur Respir J 10:219–225PubMedCrossRefGoogle Scholar
  15. 15.
    Wang NS (1975) The preformed stomas connecting the pleural cavity and the lymphatics in the parietal pleura. Am Rev Respir Dis 111:12–20PubMedGoogle Scholar
  16. 16.
    Agostoni E, Bodega F, Zocchi L (2002) Albumin transcytosis from the pleural space. J Appli Physiol 93:1806–1812Google Scholar
  17. 17.
    Song Y, Yang B, Matthay MA, Ma T, Verkman AS (2000) Role of aquaporin water channels in pleural fluid dynamics. Am J Physiol—Cell Physiol 279:C1744–C1750Google Scholar
  18. 18.
    Meyer PC (1966) Metastatic carcinoma of the pleura. Thorax 21:437–443PubMedCrossRefGoogle Scholar
  19. 19.
    Light R (1997) Diseases of the pleura. Curr Opin Pulm Medicine 3:303–304CrossRefGoogle Scholar
  20. 20.
    Yano S, Shinohara H, Herbst RS, Kuniyasu H, Bucana CD, et al (2000) Production of experimental malignant pleural effusions is dependent on invasion of the pleura and expression of vascular endothelial growth factor/vascular permeability factor by human lung cancer cells. Am J Pathol 157:1893–1903PubMedCrossRefGoogle Scholar
  21. 21.
    Yeh HH, Lai WW, Chen HH, Liu HS, Su WC (2006) Autocrine IL-6-induced Stat3 activation contributes to the pathogenesis of lung adenocarcinoma and malignant pleural effusion. Oncogene 25:4300–4309PubMedCrossRefGoogle Scholar
  22. 22.
    Stathopoulos GT, Zhu Z, Everhart MB, Kalomenidis I, Lawson WE, et al (2006) Nuclear factor-kappaB affects tumor progression in a mouse model of malignant pleural effusion. Am J Respir Cell Mol Biol 34:142–150PubMedCrossRefGoogle Scholar
  23. 23.
    Stathopoulos GT, Kollintza A, Moschos C, Psallidas I, Sherrill TP, et al (2007) Tumor necrosis factor-α promotes malignant pleural effusion. Cancer Res 67:9825–9834PubMedCrossRefGoogle Scholar
  24. 24.
    Stathopoulos GT, Psallidas I, Moustaki A, Moschos C, Kollintza A, et al (2008) A central role for tumor-derived monocyte chemoattractant protein-1 in malignant pleural effusion. J Natl Cancer Inst 100:1464–1476PubMedCrossRefGoogle Scholar
  25. 25.
    Ishimoto O, Saijo Y, Narumi K, Kimura Y, Ebina M, et al (2002) High level of vascular endothelial growth factor in hemorrhagic pleural effusion of cancer. Oncology 63:70–75PubMedCrossRefGoogle Scholar
  26. 26.
    Collins PD, Connolly DT, Williams TJ (1993) Characterization of the increase in vascular permeability induced by vascular permeability factor in vivo. Br J Pharmacol 109:195–199PubMedCrossRefGoogle Scholar
  27. 27.
    Stathopoulos GT, Psallidas I, Moustaki A, Moschos C, Kollintza A, et al (2008) A central role for tumor-derived monocyte chemoattractant protein-1 in malignant pleural effusion. J Nat Cancer Inst 100:1464–1476PubMedCrossRefGoogle Scholar
  28. 28.
    Stathopoulos G (2011) Translational advances in pleural malignancies. Respirology 16:53–63PubMedCrossRefGoogle Scholar
  29. 29.
    Light R (2007) Pleural disease. In: Evidence-based respiratory medicine, 2nd edn. Blackwell, LondonGoogle Scholar
  30. 30.
    Yeh HH, Lai WW, Chen HHW, Liu HS, Su WC (2006) Autocrine IL-6-induced Stat3 activation contributes to the pathogenesis of lung adenocarcinoma and malignant pleural effusion. Oncogene 25:4300–4309PubMedCrossRefGoogle Scholar
  31. 31.
    Boehle AS, Dohrmann P, Leuschner I, Kalthoff H, Henne-Bruns D (2000) An improved orthotopic xenotransplant procedure for human lung cancer in SCID bg mice. The Annals of Thoracic Surgery 69:1010–1015PubMedCrossRefGoogle Scholar
  32. 32.
    Edakuni N, Ikuta K, Yano S, Nakataki E, Muguruma H, et al (2006) Restored expression of the MYO18B gene suppresses orthotopic growth and the production of bloody pleural effusion by human malignant pleural mesothelioma cells in SCID mice. Oncol Res 16:235–243PubMedGoogle Scholar
  33. 33.
    Ohta Y, Kimura K, Tamura M, Oda M, Tanaka M, et al (2001) Biological characteristics of carcinomatosa pleuritis in orthotopic model systems using immune-deficient rats. Int J Oncol 18:499–505PubMedGoogle Scholar
  34. 34.
    Jongsma J, van Montfort E, Vooijs M, Zevenhoven J, Krimpenfort P, et al (2008) A conditional mouse model for malignant mesothelioma. Cancer cell 13:261–271Google Scholar
  35. 35.
    Kimura K, Nishimura H, Matsuzaki T, Yokokura T, Nimura Y, et al (2000) Synergistic effect of interleukin-15 and interleukin-12 on antitumor activity in a murine malignant pleurisy model. Cancer Immunol Immunother 49:71–77PubMedCrossRefGoogle Scholar
  36. 36.
    Hatton MWC, Southward SMR, Ross BL, Legault K, Marien L, et al (2002) Angiostatin II is the predominant glycoform in pleural effusates of rabbit VX-2 lung tumors. J Lab Clin Med 139:316–323PubMedCrossRefGoogle Scholar
  37. 37.
    Hatton MWC, Southward SMR, Legault KJ, Ross BL, Clarke BJ, et al (2004) Fibrinogen catabolism within the procoagulant VX-2 tumor of rabbit lung in vivo: effluxing fibrin(ogen) fragments contain antiangiogenic activity. J Lab Clin Med 143:241–254PubMedCrossRefGoogle Scholar
  38. 38.
    Hatton MWC, Southward SMR, Ross BL, Clarke BJ, Singh G, et al (2006) Relationships among tumor burden, tumor size, and the changing concentrations of fibrin degradation products and fibrinolytic factors in the pleural effusions of rabbits with VX2 lung tumors. J Lab Clin Med 147:27–35PubMedCrossRefGoogle Scholar
  39. 39.
    Tufan AC, Satiroglu-Tufan NL (2005) The chick embryo chorioallantoic membrane as a model system for the study of tumor angiogenesis, invasion and development of anti-angiogenic agents. Curr Cancer Drug Targets 5:249–266PubMedCrossRefGoogle Scholar
  40. 40.
    Ribatti D (2012) Chicken chorioallantoic membrane angiogenesis model. Methods Mol Biol 843:47–57PubMedGoogle Scholar
  41. 41.
    Psallidas I, Stathopoulos GT, Maniatis NA, Magkouta S, Moschos C, et al. (2013) Secreted phosphoprotein-1 directly provokes vascular leakage to foster malignant pleural effusion. Oncogene 32(4):528–535Google Scholar
  42. 42.
    Slack-Davis JK, Atkins KA, Harrer C, Hershey ED, Conaway M (2009) Vascular cell adhesion molecule-1 is a regulator of ovarian cancer peritoneal metastasis. Cancer Res 69:1469–1476PubMedCrossRefGoogle Scholar
  43. 43.
    Astoul P, Colt HG, Wang X, Hoffman RM (1993) Metastatic human pleural ovarian cancer model constructed by orthotopic implantation of fresh histologically-intact patient carcinoma in nude mice. Anticancer Res 13:1999–2002PubMedGoogle Scholar
  44. 44.
    Wang X, Fu X, Kubota T, Hoffman RM (1992) A new patient-like metastatic model of human small-cell lung cancer constructed orthotopically with intact tissue via thoracotomy in nude mice. Anticancer Res 12:1403–1406PubMedGoogle Scholar
  45. 45.
    Elkin M, Vlodavsky I (2001) Tail vein assay of cancer metastasis. Curr Protoc Cell Biol 19:2PubMedGoogle Scholar
  46. 46.
    Mase K, Iijima T, Nakamura N, Takeuchi T, Onizuka M, et al. (2002) Intrabronchial orthotopic propagation of human lung adenocarcinoma–characterizations of tumorigenicity, invasion and metastasis. Lung Cancer 36:271–276PubMedCrossRefGoogle Scholar
  47. 47.
    Heike Y, Takahashi M, Ohira T, Naruse I, Hama S, et al. (1997) Genetic immunotherapy by intrapleural, intraperitoneal and subcutaneous injection of IL-2 gene-modified Lewis lung carcinoma cells. Int J Cancer 73:844–849PubMedCrossRefGoogle Scholar
  48. 48.
    Zocchi L (2002) Physiology and pathophysiology of pleural fluid turnover. Eur Respir J 20:1545–1558PubMedCrossRefGoogle Scholar
  49. 49.
    Michailova KN, Usunoff KG (2006) Serosal membranes (pleura, pericardium, peritoneum). Normal structure, development and experimental pathology. Adv Anat Embryol Cell Biol 183:i-vii, 1–144. (back cover)Google Scholar
  50. 50.
    Yano S, Herbst RS, Shinohara H, Knighton B, Bucana CD, et al (2000) Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation. Clin Cancer Res 6(3):957–965Google Scholar
  51. 51.
    Monk JP, Phillips G, Waite R, Kuhn J, Schaaf LJ, et al (2006) Assessment of tumor necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemotherapy in cancer patients. J Clin Oncology 24(12):1852–1859Google Scholar
  52. 52.
    Abushamaa AM, Sporn TA, Folz RJ (2002) Oxidative stress and inflammation contribute to lung toxicity after a common breast cancer chemotherapy regimen. Am J Physiol Lung Cell Mol Physiol 283:L336–345PubMedGoogle Scholar
  53. 53.
    Richmond A, Su Y Mouse xenograft models vs GEM models for human cancer therapeutics: Dis Model Mech. 2008 Sep-Oct;1(2–3):78–82Google Scholar
  54. 54.
    Kim K-U, Wilson SM, Abayasiriwardana KS, Collins R, Fjellbirkeland L, et al (2005) A novel in vitro model of human mesothelioma for studying tumor biology and apoptotic resistance. pp. 541–548Google Scholar
  55. 55.
    Kraus-Berthier L, Jan M, Guilbaud N, Naze M, Pierré A, et al (2000) Histology and sensitivity to anticancer drugs of two human non-small cell lung carcinomas implanted in the pleural cavity of nude mice. Clin Cancer Res 6:297–304PubMedGoogle Scholar
  56. 56.
    Antunes G, Neville E, Duffy J, Ali N (2003) BTS guidelines for the management of malignant pleural effusions. Thorax 58:ii29–ii38Google Scholar
  57. 57.
    Kroczynska B, Cutrone R, Bocchetta M, Yang H, Elmishad AG, et al (2006) Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters. Proc Nat Acad Sci 103:14128–14133PubMedCrossRefGoogle Scholar
  58. 58.
    Kleymenova EV, Bianchi AA, Kley N, Pylev LN, Walker CL (1997) Characterization of the rat neurofibromatosis 2 gene and its involvement in asbestos-induced mesothelioma. Molecular Carcinogenesis 18:54–60PubMedCrossRefGoogle Scholar
  59. 59.
    Cui R, Takahashi F, Ohashi R, Yoshioka M, Gu T, et al (2009) Osteopontin is involved in the formation of malignant pleural effusion in lung cancer. Lung cancer (Amsterdam, Netherlands) 63:368–374Google Scholar
  60. 60.
    Hsia CC, Hyde DM, Ochs M, Weibel ER (2010) An official research policy statement of the American thoracic society/European respiratory society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med 181:394–418PubMedCrossRefGoogle Scholar
  61. 61.
    Malek A, Catapano CV, Czubayko F, Aigner A (2010) A sensitive polymerase chain reaction-based method for detection and quantification of metastasis in human xenograft mouse models. Clin Exp Metastasis 27:261–271PubMedCrossRefGoogle Scholar
  62. 62.
    Lyons SK (2005) Advances in imaging mouse tumour models in vivo. J Pathol 205:194–205PubMedCrossRefGoogle Scholar
  63. 63.
    Stathopoulos GT, Sherrill TP, Han W, Sadikot RT, Yull FE, et al. (2008) Host nuclear factor-kappaB activation potentiates lung cancer metastasis. Mol Cancer Res 6:364–371PubMedCrossRefGoogle Scholar
  64. 64.
    Zebrowski BK, Yano S, Liu W, Shaheen RM, Hicklin DJ, et al. (1999) Vascular endothelial growth factor levels and induction of permeability in malignant pleural effusions. Clin Cancer Res 5(11):3364–3368Google Scholar
  65. 65.
    Moschos C, Psallidas I, Kollintza A, Karabela S, Papapetropoulos A, et al. (2009) The angiopoietin/Tie2 axis mediates malignant pleural effusion formation. Neoplasia 11:298–304PubMedGoogle Scholar
  66. 66.
    Stathopoulos GT, Sherrill TP, Karabela SP, Goleniewska K, Kalomenidis I, et al (2010) Host-derived Interleukin-5 Promotes Adenocarcinoma-induced Malignant Pleural Effusion. Am J Respir Crit Care Med 182:1273–1281PubMedCrossRefGoogle Scholar
  67. 67.
    Zhang J, Xie C, Zhu Z, Huang H, Zeng Z Potential role of AQP1 and VEGF in the development of malignant pleural effusion in mice. Med Oncol 2012 29(2):656–662Google Scholar
  68. 68.
    Stathopoulos GT, Moschos C, Loutrari H, Kollintza A, Psallidas I, et al (2008) Zoledronic Acid Is Effective against Experimental Malignant Pleural Effusion. Am J Respir Crit Care Med 178:50–59PubMedCrossRefGoogle Scholar
  69. 69.
    Psallidas I, Karabela SP, Moschos C, Sherrill TP, Kollintza A, et al (2010) Specific effects of bortezomib against experimental malignant pleural effusion: a preclinical study. Mol Cancer 9:56PubMedCrossRefGoogle Scholar
  70. 70.
    Moschos C, Psallidas I, Cottin T, Kollintza A, Papiris S, et al (2011) A sulindac analogue is effective against malignant pleural effusion in mice. Lung Cancer 73:171–175PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Physiology, Faculty of MedicineUniversity of PatrasPatrasGreece

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