Skip to main content

Organotypic Models of Metastasis: A Three-dimensional Culture Mimicking the Human Peritoneum and Omentum for the Study of the Early Steps of Ovarian Cancer Metastasis

  • Chapter
  • First Online:
Ovarian Cancer

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Tan D, Agarwal R, Kaye SB. Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet. 2006;7:925–934.

    Article  Google Scholar 

  2. Landen C, Birrer MJ, Sood AK. Early events in the pathogenesis of epithelial ovarian cancer. J Clin Oncol. 2008;26(6):995–1005.

    Article  PubMed  Google Scholar 

  3. Agarwal R, Kaye S. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003;3(7):502–516.

    Article  CAS  PubMed  Google Scholar 

  4. Doig T, Monaghan H. Sampling the omentum in ovarian neoplasia: when one block is enough. Int J Gynecol Cancer. 2006;16:36–40.

    Article  CAS  PubMed  Google Scholar 

  5. Fidler IJ. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer. 2003;5:355–366.

    Google Scholar 

  6. Kenny HA, Krausz T, Yamada SD, Lengyel E. Development of an organotypic peritoneal three-dimensional culture to study peritoneal attachment of ovarian cancer cells. Int J Cancer. 2007;121(7):1463–1472.

    Article  CAS  PubMed  Google Scholar 

  7. Wilkosz S, Ireland G, Khwaja N, et al. A comparative study of the structure of human and murine greater omentum. Anat Embryol. 2005;209:251–261.

    Article  PubMed  Google Scholar 

  8. Liebermann-Meffert D. The greater omentum, anatomy, embryology, and surgical applications. Surg Clin North Am. 2000;80(1):275–293.

    Article  CAS  PubMed  Google Scholar 

  9. Lieberman-Meffert D. The greater omentum, anatomy, physiology, pathology and surgery with a historical survey. New York, Berlin Heidelberg: Springer; 1985:3–30.

    Google Scholar 

  10. Daya D, McCaughy WT. Pathology of the peritoneum: a review of selected topics. Semin Diagn Pathol. 1991;8(4):277–289.

    CAS  PubMed  Google Scholar 

  11. Leung JC, Chan LY, Li FF, et al. Glucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: the role of VEGF. Nephrol Dial Transplant. 2005;20(7):1336–1349.

    Article  CAS  PubMed  Google Scholar 

  12. Liaw YS, Yu CJ, Shun CT, et al. Expression of integrins in human cultured mesothelial cells: the roles in cell-to-extracellular matrix adhesion and inhibition by RGD-containing peptide. Respir Med. 2001;95(3):221–226.

    Article  CAS  PubMed  Google Scholar 

  13. Strobel T, Swanson L, Cannistra SA. In vivo inhibition of CD44 limits intra-abdominal spread of a human ovarian cancer xenograft in nude mice: a novel role for CD 44 in the process of peritoneal implantation. Cancer Res. 1997;57:1228–1232.

    CAS  PubMed  Google Scholar 

  14. Strobel T, Cannistra SA. β1-integrins partly mediate binding of ovarian cancer cells to peritoneal mesothelium in vitro. Gynecol Oncol. 1999;73:362–367.

    Article  CAS  PubMed  Google Scholar 

  15. Lessan K, Aguiar D, Oegema TR, Siebenson L, Skubitz AP. CD44 and β1 integrin mediate ovarian carcinoma cell adhesion to peritoneal mesothelial cells. Am J Pathol. 1999;154(5):1525–1537.

    CAS  PubMed  Google Scholar 

  16. Ahmed N, Riley C, Rice G, Quinn M. Role of integrin receptors for fibronectin, collagen and laminin in the regulation of ovarian carcinoma functions in response to a matrix microenvironment. Clin Exp Metastasis. 2005;22:391–402.

    Article  CAS  PubMed  Google Scholar 

  17. Rieppi M, Vergani V, Gatto C, et al. Mesothelial cells induce the motility of human ovarian carcinoma cells. Int J Cancer. 1999;80:303–307.

    Article  CAS  PubMed  Google Scholar 

  18. Sawada K, Radjabi AR, Bhaskar V, et al. Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res. 2008;68(7):2329–2339.

    Article  CAS  PubMed  Google Scholar 

  19. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nature. 2006;6:392–401.

    CAS  Google Scholar 

  20. Mueller M, Fusenig N. Friends or foes – bipolar effects of the tumour stroma in cancer. Nat Rev. 2004;4:839–849.

    Article  CAS  Google Scholar 

  21. Witz C, Montoya-Rodriguez I, Cho S, Centonze V, Bonewald L, Schenken R. Composition of the extracellular matrix of the peritoneum. J Soc Gynecol Investig. 2001;8(5):299–304.

    Article  CAS  PubMed  Google Scholar 

  22. Kenny HA, Kaur S, Coussens L, Lengyel E. The initial steps of ovarian cancer cell metastasis are mediated by MMP-2 cleavage of vitronectin and fibronectin. J Clin Invest. 2008;118(4):1367–1379.

    Article  CAS  PubMed  Google Scholar 

  23. Moser TL, Pizzo SV, Bafetti L, Fishman DA, Stack MS. Evidence for preferential adhesion of ovarian epithelial carcinoma cells to type I collagen mediated by the α2β1 integrin. Int J Cancer. 1996;67:695–701.

    Article  CAS  PubMed  Google Scholar 

  24. Zhu G, Risteli J, Puistola U, Kauppila A, Risteli L. Progressive ovarian carcinoma induces synthesis of type 1 and type III procollagens in the tumor tissue and peritoneal cavity. Cancer Res. 1993;53:5028–5032.

    CAS  PubMed  Google Scholar 

  25. Cannistra SA, Ottensmeier C, Niloff J, Orta B, DiCarlo J. Expression and function of β1 and αvβ3 integrins in ovarian cancer. Gynecol Oncol. 1995;58:216–225.

    Article  CAS  PubMed  Google Scholar 

  26. Symowicz J, Adley BP, Gleason KJ, et al. Engagement of collagen-binding integrins promotes matrix metalloproteinase-9-dependent E-cadherin ectodomain shedding in ovarian carcinoma cells. Cancer Res. 2007;67(5):2030–2039.

    Article  CAS  PubMed  Google Scholar 

  27. Barbolina MV, Adley BP, Ariztia EV, Liu Y, Stack MS. Microenvironmental regulation of membrane type 1 matrix metalloproteinase activity in ovarian carcinoma cells via collagen-induced EGR1 expression. J Biol Chem. 2007;282(7):4924–4931.

    Article  CAS  PubMed  Google Scholar 

  28. Ellerbroek SM, Wu YI, Overall CM, Stack MS. Functional interplay between type I collagen and cell surface matrix metalloproteinase activity. J Biol Chem. 2001;276:24833–24842.

    Article  CAS  PubMed  Google Scholar 

  29. Fishman DA, Liu Y, Ellerbroek SM, Stack MS. Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP-dependent invasion in ovarian cancer cells. Cancer Res. 2001;61(7):3194–3199.

    CAS  PubMed  Google Scholar 

  30. Fishman DA, Kearns AS, Chilukuri K, et al. Metastatic dissemination of human ovarian epithelial carcinoma is promoted by a α2β1-integrin-mediated interaction with type I collagen. Invasion Metastasis. 1998;18:15–26.

    Article  CAS  PubMed  Google Scholar 

  31. Ellerbroek SM, Fishman DA, Kearns AS, Bafetti L, Stack MS. Ovarian carcinoma regulation of matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase through β1 integrin. Cancer Res. 1999;59:1635–1641.

    CAS  PubMed  Google Scholar 

  32. Moser TL, Young TN, Rodriguez GC, Pizzo SV, Bast RC, Stack MS. Secretion of extracellular matrix-degrading proteinases is increased in epithelial ovarian carcinoma. Int J Cancer. 1994;56:552–559.

    Article  CAS  PubMed  Google Scholar 

  33. Cheng K, Lahad J, Kuo W, et al. The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med. 2004;10(11):1251–1256.

    Article  CAS  PubMed  Google Scholar 

  34. Shayesteh L, Lu Y, Kuo W, et al. PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet. 1999;21:99–102.

    Article  CAS  PubMed  Google Scholar 

  35. Debnath J, Mills KR, Collins NL, Reginato MJ, Muthuswamy SK, Brugge JS. The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell. 2002;111:29–40.

    Article  CAS  PubMed  Google Scholar 

  36. Beningo K, Dembo M, Wanf Yu. Responses of fibroblasts to anchorage of dorsal extracellular matrix receptors. Proc Natl Acad Sci USA. 2004;101(52):18024–18029.

    Article  CAS  PubMed  Google Scholar 

  37. Sawada M, Shii J, Akedo H, Tanizawa O. An experimental model for ovarian tumor invasion of cultured mesothelial cell monolayer. Lab Invest. 1994;70(3):333–338.

    CAS  PubMed  Google Scholar 

  38. Westerlund A, Hujanen E, Puistola U, Turpeenniemi-Hujanen T. Fibroblasts stimulate human ovarian cancer cell invasion and expression of 72-kDa gelatinase A (MMP-2). Gynecol Oncol. 1997;67:76–82.

    Article  CAS  PubMed  Google Scholar 

  39. Boyd R, Balkwill F. MMP-2 release and activation in ovarian carcinoma: the role of fibroblasts. Br J Cancer. 1999;80:315–321.

    Article  CAS  PubMed  Google Scholar 

  40. Rygaard J, Povlsen CO. Heterotransplantation of a human malignant tumor to “Nude” mice. Acta Pathol Microbiol Scand. 1969;77(4):758–760.

    Article  CAS  PubMed  Google Scholar 

  41. Voskoglou-Nomikos T, Pater JL, Seymour L. Clinical predicitive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res. 2003;9:4227–4239.

    PubMed  Google Scholar 

  42. Bissell MJ, Hall HG, Parry G. How does the extracellular matrix direct gene expression. J Theor Biol. 1982;99:31–68.

    Article  CAS  PubMed  Google Scholar 

  43. Niedbala MJ, Crickard K, Bernacki R. In vitro degradation of extracellular matrix by human ovarian carcinoma cells. Clin Exp Metastasis. 1987;5(2):181–197.

    Article  CAS  PubMed  Google Scholar 

  44. Kanemoto T, Martin GR, Hamilton TC, Fridman R. Effects of synthetic peptides and protease inhibitors on the interaction of a human ovarian cancer cell line (NIH:OVCAR-3) with a reconstituted basement membrane (matrigel). Invasion Metastasis. 1991;11:84–92.

    CAS  PubMed  Google Scholar 

  45. Burleson KM, Boente MP, Pambuccian SE, Skubitz AP. Disaggregation and invasion of ovarian carcinoma ascites spheroids. J Transl Med. 2006;24:4–6.

    Google Scholar 

  46. Burleson KM, Casey RC, Skubitz KM, Pambuccian SE, Oegema TR, Skubitz AP. Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol Oncol. 2004;93:170–181.

    Article  CAS  PubMed  Google Scholar 

  47. Burleson KM, Hansen LK, Skubitz AP. Ovarian carcinoma spheroids disaggregate on type I collagen and invade live human mesothelial cell monolayers. Clin Exp Metastasis. 2004;21(8):685–697.

    Article  CAS  PubMed  Google Scholar 

  48. Casey RC, Skubitz AP. CD44 and β1 integrins mediate ovarian carcinoma cell migration toward extracellular matrix proteins. Clin Exp Metastasis. 2000;18:67–75.

    Article  CAS  PubMed  Google Scholar 

  49. Casey RC, Oegema TR, Skubitz KM, Pambuccian SE, Grindle SM, Skubitz AP. Cell membrane glycosylation mediates the adhesion, migration, and invasion of ovarian carcinoma cells. Clin Exp Metastasis. 2003;20(2):143–152.

    Article  CAS  PubMed  Google Scholar 

  50. Casey RC, Koch KA, Oegema TR, et al. Establishment of an in vitro assay to measure the invasion of ovarian carcinoma cells through mesothelial cell monolayers. Clin Exp Metastasis. 2003;20:343–356.

    Article  CAS  PubMed  Google Scholar 

  51. Casey RC, Burleson KM, Skubitz KM, et al. β1-integrins regulate the formation and adhesion of ovarian carcinoma multicellular spheroids. Am J Pathol. 2001;159:2071–2080.

    CAS  PubMed  Google Scholar 

  52. Skubitz AP, Bast RC, Wayner EA, Letourneau PC, Wilke MS. Expression of α6 and β4 integrins in serous ovarian carcinoma correlates with expression of the basement membrane protein laminin. Am J Pathol. 1996;148(5):1445–1461.

    CAS  PubMed  Google Scholar 

  53. Barbolina MV, Adley BP, Shea LD, Stack MS. Wilms tumor gene protein 1 is associated with ovarian cancer metastasis and modulates cell invasion. Cancer. 2007;112(7):1632–1641.

    Article  Google Scholar 

  54. Suzuki N, Aoki D, Tamada Y, et al. HMOCC-1, a human monoclonal antibody that inhibits adhesion of ovarian cancer cells to human mesothelial cells. Gynecol Oncol. 2004;95:290–298.

    Article  CAS  PubMed  Google Scholar 

  55. Kishikawa T, Sakamoto M, Ino Y, Kubushiro K, Nozawa S, Hirohashi S. Two distinct pattern of peritoneal involvement shown by in vitro and in vivo ovarian cancer dissemination models. Invasion Metastasis. 1995;15:11–21.

    CAS  PubMed  Google Scholar 

  56. Niedbala MJ, Crickard K, Bernacki R. Interactions of human ovarian tumor cells with human mesothelial cells grown on extracellular matrix. An in vitro model system for studying tumor cell adhesion and invasion. Exp Cell Res. 1985;160(2):499–513.

    Article  CAS  PubMed  Google Scholar 

  57. Weaver VM, Fischer A, Peterson O, Bissell MJ. The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay. Biochem Cell Biol. 1996;74(6):833–851.

    Article  CAS  PubMed  Google Scholar 

  58. Weaver VM, Petersen OW, Wang F, et al. Revision of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J Cell Biol. 1997;137(1):231–245.

    Article  CAS  PubMed  Google Scholar 

  59. Park CC, Zhang H, Pallavicini M, et al. β1 Integrin inhibitory antibody induces apoptosis of breast cancer cells, inhibits growths, and distinguishes malignant from normal phenotype in three dimensional cultures and in vivo. Cancer Res. 2006;66(3):1526–1535.

    Article  CAS  PubMed  Google Scholar 

  60. Weaver VM, Howlett AR, Langton-Webster B, Petersen O, Bissell M. The development of a functionally relevant cell culture model of progressive human breast cancer. Semin Cancer Biol. 1995;6(3):175–184.

    Article  CAS  PubMed  Google Scholar 

  61. Wang F, Weaver VM, Petersen OW, et al. Reciprocal interactions between β1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology. Proc Natl Acad Sci USA. 1998;95:14821–14826.

    Article  CAS  PubMed  Google Scholar 

  62. Rizki A, Weaver VM, Lee SY, et al. A human breast cell model of preinvasive to invasive transition. Cancer Res. 2008;68(5):1378–1387.

    Article  CAS  PubMed  Google Scholar 

  63. Lee GY, Kenny PA, Lee EH, Bissel MJ. Three-dimensional culture models of normal and malignant breast epithelial cells. Nat Methods. 2007;4(4):359–365.

    Article  CAS  PubMed  Google Scholar 

  64. Peterson OW, Ronnov-Jessen L, Bissell MJ. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant breast epithelial cells. Proc Natl Acad Sci USA. 1992;89(19):9064–9068.

    Article  Google Scholar 

  65. Roskelley CD, Desprez PY, Bissell MJ. Extracellular matrix-dependent tissue-specific gene expression in mammary epithelial cells requires both physical and biochemiacal signal transduction. Proc Natl Acad Sci USA. 1994;91:12378–12382.

    Article  CAS  PubMed  Google Scholar 

  66. Zutter MM, Santoro SA, Staatz WD, Tsung YL. Re-expression of the α2β1-integrin abrogates the malignant phenotype of breast carcinoma cells. Proc Natl Acad Sci USA. 1995;92:7411–7415.

    Article  CAS  PubMed  Google Scholar 

  67. Berking C, Herlyn M. Human skin reconstruct models: a new application for studies of melanocyte and melanoma biology. Histo Histopathol. 2001;16:669–674.

    CAS  Google Scholar 

  68. Meier FE, Nesland M, Hsu M, et al. Human melanoma progression in skin reconstructs. Am J Pathol. 2000;156(1):193–200.

    CAS  PubMed  Google Scholar 

  69. Haass NK, Smalley KS, Li L, Hermes M. Adhesion, migration and communication in melanocytes and melanoma. Pigment Cell Res. 2005;18(3):150–159.

    Article  CAS  PubMed  Google Scholar 

  70. Auersperg N, Ota T, Mitchell GW. Early events in ovarian epithelial carcinogenesis progress and problems in experimental approaches. Int J Gynecol Cancer. 2002;12:691–703.

    Article  CAS  PubMed  Google Scholar 

  71. Puiffe ML, Le Page C, Filali-Mouhim A et al. Characterization of ovarian cancer ascites on cell invasion, proliferation, spheroid formation, and gene expression in an in vitro model of epithelial ovarian cancer. Neoplasia. 2007;9(10):820–829.

    Article  CAS  PubMed  Google Scholar 

  72. Hotary KB, Li X, Allen E, Stevens SL, Weiss SJ. A cancer cell metalloprotease triad regulates the basement membrane transmigration program. Genes Dev. 2006;20:2673–2686.

    Article  CAS  PubMed  Google Scholar 

  73. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006;66(2):605–612.

    Article  CAS  PubMed  Google Scholar 

  74. Lu M, Gao R, Xiao L, Wang Z. Construction of three-dimensional in vitro culture model of ovarian carcinoma and the study of its multicellular drug resistance. J Huazhong Univ Sci Technol Med Sci. 2006;26(6):741–743.

    Article  CAS  PubMed  Google Scholar 

  75. Zietarska M, Maugard C, Filali-Mouhim A, et al. Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC). Mol Carcinog. 2007;46:872–885.

    Article  CAS  PubMed  Google Scholar 

  76. Kurman R, Visvanathan K, Roden R, Wu TC, Shih I-M. Early detection and treatment of ovarian cancer: shifting from early stage to minimal volume of disease based on a new model of carcinogenesis. J Obstet Gynecol. 2008;351–356.

    Google Scholar 

Download references

Acknowledgments

The development of the 3D ovarian cancer culture was supported over the years through grants to Ernst Lengyel from the Gynecologic Cancer Foundation (2005/2006 GCF/Molly Cade Ovarian Cancer Research Grant), the Ovarian Cancer Research Fund (OCRF, Liz Tilberis Scholars Program), and the NCI (R01 CA111882). Ernst Lengyel holds a Clinical Scientist Award in Translational Research from the Burroughs Wellcome Fund. Hilary A. Kenny was supported by a Penny Severns Breast, Cervical, and Ovarian Cancer Research postdoctoral fellowship from the Illinois Department of Public Health and a Graduate Training Program in Cancer Biology postdoctoral fellowship through the University of Chicago (NIH/NCI 5T32 CA09594). Songuel Dogan was supported by the Deutsche Forschungsgemeinschaft (German Research Council) DOI309/1–1. Marion Zillhardt was supported by the Graduate Training Program in Cancer Biology through the University of Chicago (NIH/NCI T32 CA09594). The authors would like to thank Gail Isenberg (University of Chicago) for her graphic designs and editorial expertise.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ernst Lengyel .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Kenny, H.A. et al. (2009). Organotypic Models of Metastasis: A Three-dimensional Culture Mimicking the Human Peritoneum and Omentum for the Study of the Early Steps of Ovarian Cancer Metastasis. In: Stack, M., Fishman, D. (eds) Ovarian Cancer. Cancer Treatment and Research, vol 149. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-98094-2_16

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-98094-2_16

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-98093-5

  • Online ISBN: 978-0-387-98094-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics