Claudin-5 and Cancer Metastasis

  • Cláudia Malheiros Coutinho-Camillo
  • Silvia Vanessa Lourenço
  • Fernando Augusto Soares
Chapter
First Online:
Part of the Cancer Metastasis - Biology and Treatment book series (CMBT, volume 19)

Abstract

The claudin family of proteins plays a critical role in the maintenance of epithelial and endothelial tight junctions, maintenance of the cytoskeleton and in cell signaling. While the exact functions of claudins in cancer cells are not fully understood, some studies suggest that claudins are involved in survival and invasion of cancer cells. Claudin-5, forming the backbone of tight junctions in blood vessels and lymphatic endothelial cells, has an important role in maintaining the homeostasis of the tissue microenvironment and tumors showing claudin-5 expression could have some additional affinity for blood vessels. Metastasis is a complex phenomenon that requires a number of specific steps such as decreased adhesion, increased motility and invasion, proteolysis, and resistance to apoptosis. Several studies about significance of claudin-5 expression in cancer cells were reported, suggesting that it may play an important role in regulation of metastasis, angiogenesis and tumor growth.

Keywords

Claudins Claudin-5 Metastasis Tumorigenesis Cancer Tight junction Cell proliferation Invasion Cell survival Cell-cell adhesion 
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References

  1. Agarwal R, D’Souza T, Morin PJ (2005) Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res 65:7378–7385PubMedCrossRefGoogle Scholar
  2. Anderson JM (2001) Molecular structure of tight junctions and their role in epithelial transport. News Physiol Sci 16:126–130PubMedGoogle Scholar
  3. Bello IO, Soini Y, Slootweg PJ, Salo T (2007) Claudins 1, 4, 5, 7 and occludin in ameloblastomas and developing human teeth. J Oral Pathol Med 36(1):48–54PubMedCrossRefGoogle Scholar
  4. Bello IO, Vilen ST, Niinimaa A, Kantola S, Soini Y, Salo T (2008) Expression of claudins 1, 4, 5, and 7 and occludin, and relationship with prognosis in squamous cell carcinoma of the tongue. Hum Pathol 39(8):1212–1220PubMedCrossRefGoogle Scholar
  5. Billings SD, Walsh SV, Fisher C, Nusrat A, Weiss SW, Folpe AL (2004) Aberrant expression of tight junction-related proteins ZO-1, claudin-1 and occludin in synovial sarcoma: an immunohistochemical study with ultrastructural correlation. Mod Pathol 17:141–149PubMedCrossRefGoogle Scholar
  6. Cheung ST, Leung KL, Ip YC, Chen X, Fong DY, Ng IO, Fan ST, So S (2005) Claudin-10 expression level is associated with recurrence of primary hepatocellular carcinoma. Clin Cancer Res 11:551–556PubMedGoogle Scholar
  7. Chiba H, Gotoh T, Kojima T et al (2003) Hepatocyte nuclear factor (HNF)-4α triggers formation of functional tight junction and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells. Exp Cell Res 286:288–297PubMedCrossRefGoogle Scholar
  8. Chiba T, Kawachi H, Kawano T, Kumagai J, Kitagaki K, Sekine M, Uchida K, Kobayashi M, Sugihara K, Eishi Y (2010) Independent histological risk factors for lymph node metastasis of superficial esophageal squamous cell carcinoma; implication of claudin-5 immunohistochemistry for expanding the indications of endoscopic resection. Dis Esophagus 23(5):398–407PubMedGoogle Scholar
  9. Coutinho-Camillo CM, Lourenço SV, da Fonseca FP, Soares FA (2011) Claudin expression is dysregulated in prostate adenocarcinomas but does not correlate with main clinicopathological parameters. Pathology 43(2):143–148PubMedCrossRefGoogle Scholar
  10. De Torres Ramirez I (2007) Prognosis and predictive factors of prostate cancer in the prostatic biopsy. Actas Urol Esp 31(9):1025–1044PubMedCrossRefGoogle Scholar
  11. Dhawan P, Singh AB, Deane NG et al (2005) Claudin-1 regulates cellular transformation and metastatic behaviour in colon cancer. J Clin Invest 115:1765–1776PubMedCrossRefGoogle Scholar
  12. Fedwick JP, Lapointe TK, Meddings JB, Sherman PM, Buret AG (2005) Helicobacter pylori activates myosin light-chain kinase to disrupt claudin-4 and claudin-5 and increase epithelial permeability. Infect Immun 73(12):7844–7852PubMedCrossRefGoogle Scholar
  13. Frixen UH, Behrens J, Sachs M et al (1991) E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol 113:173–185PubMedCrossRefGoogle Scholar
  14. Furuse M (2010) Molecular basis of the core structure of tight junctions. Cold Spring Harb Perspect Biol 2(1):a002907PubMedCrossRefGoogle Scholar
  15. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (1998) Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occluding. J Cell Biol 41:1539–1550CrossRefGoogle Scholar
  16. Furuse M, Sasaki H, Tsukita S (1999) Manner of interaction of heterogenous claudin species within and between tight junction strands. J Cell Biol 147:891–903PubMedCrossRefGoogle Scholar
  17. Gonzalez-Mariscal L, Betanzos A, Nava P, Jaramillo BE (2003) Tight junction proteins. Prog Biophys Mol Biol 81:1–44PubMedCrossRefGoogle Scholar
  18. Hewitt KJ, Agarwal R, Morin PJ (2006) The claudin gene family: expression in normal and neoplastic tissues. BMC Cancer 6:186PubMedCrossRefGoogle Scholar
  19. Hirohashi S (1998) Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153:333–339PubMedCrossRefGoogle Scholar
  20. Kominsky SL (2006) Claudins: emerging targets for cancer therapy. Expert Rev Mol Med 8(18):1–11PubMedCrossRefGoogle Scholar
  21. Langbein L, Grund C, Kuhn C et al (2002) Tight junctions and compositionally related junctional structures in mammalian stratified epithelia and cell cultures derived therefrom. Eur J Cell Biol 81:419–435PubMedCrossRefGoogle Scholar
  22. Lee JW, Lee SJ, Seo J et al (2005) Increased expressions of claudin-1 and claudin-7 during the progression of cervical neoplasia. Gynecol Oncol 97:53–59PubMedCrossRefGoogle Scholar
  23. Lourenço SV, Coutinho-Camillo CM, Buim ME, Pereira CM, Carvalho AL, Kowalski LP, Soares FA (2010) Oral squamous cell carcinoma: status of tight junction claudins in the different histopathological patterns and relationship with clinical parameters. A tissue-microarray-based study of 136 cases. J Clin Pathol 63(7):609–614PubMedCrossRefGoogle Scholar
  24. Marchesi F, Piemonti L, Mantovani A, Allavena P (2010) Molecular mechanisms of perineural invasion, a forgotten pathway of dissemination and metastasis. Cytokine Growth Factor Rev 21(1):77–82PubMedCrossRefGoogle Scholar
  25. Martin TA, Jiang WG (2009) Loss of tight junction barrier function and its role in cancer metastasis. Biochim Biophys Acta 1788(4):872–891PubMedCrossRefGoogle Scholar
  26. Martin TA, Mansel RE, Jiang WG (2002) Antagonistic effect of NK4 on HGF/SF induced changes in the transendothelial resistance (TER) and paracellular permeability of human vascular endothelial cells. J Cell Physiol 192(3):268–275PubMedCrossRefGoogle Scholar
  27. Martin TA, Watkins G, Mansel RE, Jiang WG (2004) Hepatocyte growth factor disrupts tight junctions in human breast cancer cells. Cell Biol Int 28(5):361–371PubMedCrossRefGoogle Scholar
  28. Masieri L, Lanciotti M, Nesi G, Lanzi F, Tosi N, Minervini A, Lapini A, Carini M, Serni S (2010) Prognostic role of perineural invasion in 239 consecutive patients with pathologically organ-confined prostate cancer. Urol Int 85(4):396–400PubMedCrossRefGoogle Scholar
  29. Michl P, Barth C, Buchholz M, Lerch M, Rolke M, Holzmann KH et al (2003) Claudin-4 expression decreases invasiveness and metastatic potential of pancreatic cancer. Cancer Res 63:6265–6271PubMedGoogle Scholar
  30. Miyamori H, Takino T, Kobayashi Y, Tokai H, Itoh Y, Seiki M, Sato H (2001) Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases. J Biol Chem 276(30):28204–28211PubMedCrossRefGoogle Scholar
  31. Morin PJ (2005) Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 65:9603–9606PubMedCrossRefGoogle Scholar
  32. Mullin JM, Laughlin KV, Ginanni N, Marano CW, Clarke HM, Peralta Soler A (2000) Increased tight junction permeability can result from protein kinase C activation/translocation and act as a tumor promotional event in epithelial cancers. Ann N Y Acad Sci 915:231–236PubMedCrossRefGoogle Scholar
  33. Mullin JM, Valenzano MC, Trembeth S, Allegretti PD, Verrecchio JJ, Schmidt JD, Jain V, Meddings JB, Mercogliano G, Thornton JJ (2006) Transepithelial leak in Barrett’s esophagus. Dig Dis Sci 51(12):2326–2336PubMedCrossRefGoogle Scholar
  34. Oku N, Sasabe E, Ueta E, Yamamoto T, Osaki T (2006) Tight junction protein claudin-1 enhances the invasive activity of oral squamous carcinoma cells by promoting cleavage of laminin-5 gamma2 chain via matrix metalloproteinase (MMP-2) an membrane-type MMP-1. Cancer Res 66:5251–5257PubMedCrossRefGoogle Scholar
  35. Oliveira SS, Morgado-Díaz JA (2007) Claudins: multifunctional players in epithelial tight junctions and their role in cancer. Cell Mol Life Sci 64(1):17–28PubMedCrossRefGoogle Scholar
  36. Ouban A, Ahmed AA (2010) Claudins in human cancer: a review. Histol Histopathol 25(1):83–90PubMedGoogle Scholar
  37. Paschoud S, Bongiovanni M, Pache JC, Citi S (2007) Claudin-1 and claudin-5 expression patterns differentiate lung squamous cell carcinomas from adenocarcinomas. Mod Pathol 20(9):947–954PubMedCrossRefGoogle Scholar
  38. Pfeiffer F, Kumar V, Butz S et al (2008) Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node. Eur J Immunol 2008(38):2142–2155CrossRefGoogle Scholar
  39. Rescigno M, Rotta G, Valzasina B, Ricciardi-Castagnoli P (2001) Dendritic cells shuttle microbes across gut epithelial monolayers. Immunobiology 204:572–581PubMedCrossRefGoogle Scholar
  40. Sakaguchi T, Suzuki S, Higashi H, Inaba K, Nakamura S, Baba S, Kato T, Konno H (2008) Expression of tight junction protein claudin-5 in tumor vessels and sinusoidal endothelium in patients with hepatocellular carcinoma. J Surg Res 147(1):123–131PubMedCrossRefGoogle Scholar
  41. Seo KW, Kwon YK, Kim BH, Kim CI, Chang HS, Choe MS, Park CH (2010) Correlation between claudins expression and prognostic factors in prostate cancer. Korean J Urol 51(4):239–244PubMedCrossRefGoogle Scholar
  42. Singh AB, Sharma A, Dhawan P (2010) Claudin family of proteins and cancer: an overview. J Oncol 2010:541957PubMedCrossRefGoogle Scholar
  43. Sobel G, Németh J, Kiss A, Lotz G, Szabó I, Udvarhelyi N, Schaff Z, Páska C (2006) Claudin 1 differentiates endometrioid and serous papillary endometrial adenocarcinoma. Gynecol Oncol 103(2):591–598PubMedCrossRefGoogle Scholar
  44. Soini Y (2004) Claudins 2, 3, 4 and 5 in Paget’s disease and breast carcinoma. Hum Pathol 35:1531–1536PubMedCrossRefGoogle Scholar
  45. Soini Y (2005) Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours. Histopathology 46:551–560PubMedCrossRefGoogle Scholar
  46. Soini Y, Talvensaari-Mattila A (2006) Expression of claudins 1, 4, 5, and 7 in ovarian tumors of diverse types. Int J Gynecol Pathol 25(4):330–335PubMedCrossRefGoogle Scholar
  47. Soini Y, Kinnula V, Kahlos K, Pääkkö P (2006a) Claudins in differential diagnosis between mesothelioma and metastatic adenocarcinoma of the pleura. J Clin Pathol 59(3):250–254PubMedCrossRefGoogle Scholar
  48. Soini Y, Tommola S, Helin H, Martikainen P (2006b) Claudins 1, 3, 4 and 5 in gastric carcinoma, loss of claudin expression associates with the diffuse subtype. Virchows Arch 448:52–58PubMedCrossRefGoogle Scholar
  49. Soler AP, Miller RD, Laughlin KV, Carp NZ, Klurfeld DM, Mullin JM (1999) Increased tight junctional permeability is associated with the development of colon cancer. Carcinogenesis 20(8):1425–1431PubMedCrossRefGoogle Scholar
  50. Sung SS, Fu SM, Rose CE Jr, Gaskin F, Ju ST, Beaty SR (2006) A major lung CD103 (alphaE)-beta7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. J Immunol 176:2161–2172PubMedGoogle Scholar
  51. Szasz AM, Tokes AM, Micsinai M, Krenacs T, Jakab C, Lukacs L, Nemeth Z, Baranyai Z, Dede K, Madaras L, Kulka J (2011) Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis. Clin Exp Metastasis 28(1):55–63PubMedCrossRefGoogle Scholar
  52. Takala H, Saarnio J, Wiik H, Soini Y (2007) Claudins 1, 3, 4, 5 and 7 in esophageal cancer: loss of claudin 3 and 4 expression is associated with metastatic behavior. APMIS 115:838–847PubMedCrossRefGoogle Scholar
  53. Tobioka H, Sawada N, Zhong Y, Mori M (1996) Enhanced paracellular barrier function of rat mesothelial cells partially protects against cancer cell penetration. Br J Cancer 74(3):439–445PubMedCrossRefGoogle Scholar
  54. Tsukita S, Furuse M (1999) Occludin and claudins in tight-junction strands: leading or supporting players? Trends Cell Biol 9:268–273PubMedCrossRefGoogle Scholar
  55. Turksen K, Troy TC (2004) Barriers built on claudins. J Cell Sci 117:2435–2447PubMedCrossRefGoogle Scholar
  56. Turksen K, Troy TC (2011) Junctions gone bad: claudins and loss of the barrier in cancer. Biochim Biophys Acta 1816(1):73–79PubMedGoogle Scholar
  57. Turunen M, Talvensaari-Mattila A, Soini Y, Santala M (2009) Claudin-5 overexpression correlates with aggressive behavior in serous ovarian adenocarcinoma. Anticancer Res 29(12):5185–5189PubMedGoogle Scholar
  58. Väre P, Soini Y (2010) Twist is inversely associated with claudins in germ cell tumors of the testis. APMIS 118(9):640–647PubMedCrossRefGoogle Scholar
  59. Väre P, Loikkanen I, Hirvikoski P et al (2008) Low claudin expression is associated with high Gleason grade in prostate adenocarcinoma. Oncol Rep 19(1):25–31PubMedGoogle Scholar
  60. Wirtz D, Konstantopoulos K, Searson PC (2011) The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer 11(7):512–522PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Cláudia Malheiros Coutinho-Camillo
    • 1
    • 2
  • Silvia Vanessa Lourenço
    • 3
    • 4
  • Fernando Augusto Soares
    • 1
    • 3
  1. 1.Department of Anatomic PathologyHospital A.C. CamargoSão PauloBrazil
  2. 2.Centro Internacional de Pesquisa e EnsinoHospital AC CamargoSão PauloBrazil
  3. 3.Discipline of General Pathology, Dental SchoolUniversity of São PauloSão PauloBrazil
  4. 4.São PauloBrazil

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