Journal of Molecular Histology

, Volume 36, Issue 1–2, pp 119–129 | Cite as

Expression of α V-associated integrin β subunits in epithelial ovarian cancer andits relation to prognosis in patients treated with platinum-based regimens

  • Sylvie Maubant
  • Séverine Cruet-Hennequart
  • Soizic Dutoit
  • Yves Denoux
  • Hubert Crouet
  • Michel Henry-Amar
  • Pascal Gauduchon


The aim of the study was to investigate the relationships between the expression of αv, β1, β3, β5, and β6, integrin subunits and clinical parameters in ovarian cancers. Ovarian surface epithelium (OSE) from five donors and tumour samples from 39 patients with an epithelial ovarian cancer (39 primary tumours and 21 associated peritoneal metastases) were analysed using immunohistochemistry on paraffin-embedded or frozen tissue sections. The αv and β5 integrin subunits were always present in normal OSE and in tumours. β1 and β3 subunit expression was significantly less frequent in grade 3 than in grade 1–2 tumours. The proportion of stage IV tumours expressing β3 was significantly lower as compared to other stages. The β6 subunit was undetectable in OSE but was expressed in about 40% of primary tumours. For all integrin, there was a strong relationship between the expression in primary tumours and in associated peritoneal metastases. Survival analyses restricted to patients receiving platinum-based chemotherapy did not reveal any relationship between integrin subunit expression and 3-year survival rate, in this limited series of patients. In conclusion, the expression of the various β integrin subunits was differentially altered in ovarian carcinoma, evocative of complementary roles of αv integrins during tumour development.


Ovarian Cancer Primary Tumour Integrin Ovarian Carcinoma Epithelial Ovarian Cancer 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agrez, M, Chen, A, Cone, RI, Pytela, R, Sheppard, D 1994The αvβ6 integrin promotes proliferation of colon carcinoma cells through a unique region of the β6 cytoplasmic domainJ Cell Biol127547556Google Scholar
  2. Ahmed, N, Pansino, F, Clyde, R, Murthi, P, Quinn, MA, Rice, GE, Agrez, MV, Mok, S, Baker, MS 2002aOverexpression of αvβ6 integrin in serous epithelial ovarian cancer regulates extracellular matrix degradation via the plasminogen activation cascadeCarcinogenesis23237244Google Scholar
  3. Ahmed, N, Riley, C, Rice, GE, Quinn, MA, Baker, MS 2002bAlpha(v)beta(6) integrin–A marker for the malignant potential of epithelial ovarian cancerJ Histochem Cytochem5013711380Google Scholar
  4. Auersperg, N, Edelson, MI, Mok, SC, Johnson, SW, Hamilton, TC 1998The biology of ovarian cancerSem Oncol25281304Google Scholar
  5. Bartolazzi, A, Kaczmarek, J, Nicolo, G, Risso, AM, Tarone, G, Rossino, P, Defilippi, P, Castellani, P 1993Localization of the α3β1 integrin in some common epithelial tumours of the ovary and in normal equivalentsAnticancer Res13112Google Scholar
  6. Beavon, IRG 2000The E-cadherin-catenin complex in tumour metastasis: structure, function and regulationEur J Cancer3616071620Google Scholar
  7. Bottini, C, Miotti, S, Fiorucci, S, Facheris, P, Ménard, S, Colnaghi, MI. 1993Polarization of the α6β4 integrin in ovarian carcinomaInt J Cancer54261267Google Scholar
  8. Cambier, S, Mu, DZ, O’Connell, D, Boylen, K, Travis, W, Liu, WH, Broaddus, VC, Nishimura, SL 2000A role for the integrin alphavbeta8 in the negative regulation of epithelial cell growthCancer Res6070847093Google Scholar
  9. Cannistra, SA, Ottensmeier, C, Niloff, J, Orta, B, DiCarlo, J 1995Expression and function of beta 1 and alpha v beta 3 integrins in ovarian cancerGynecol Oncol58216225Google Scholar
  10. Carreiras, F, Denoux, Y, Staedel, C, Lehmann, M, Sichel, F, Gauduchon, P 1996Expression and localisation of αv integrins and of their ligand vitronectin in normal ovarian epithelium and in ovarian carcinomaGynecol Oncol62260267Google Scholar
  11. Carreiras, F, Rigot, V, Cruet, S, André, F, Gauduchon, P, Marvaldi, J 1999Migration properties of the human ovarian adenocarcinoma cell line IGROV 1: importance of αvβ3 integrins and vitronectinInt J Cancer80285294Google Scholar
  12. Clezardin, P 1998Recent insight into the role of integrins in cancer metastasisCell Mol Life Sci54541554Google Scholar
  13. Coppolino, MG, Dedhar, S. 2000Bi-directional signal transduction by integrins receptorsInt J Biochem Cell Biol32171188Google Scholar
  14. Cruet, S, Carreiras, F, Staedel, C, Gauduchon, P 1999Adhesion molecules and proteases in epithelial ovarian cancersMed Sci15645654Google Scholar
  15. Cruet-Hennequart, S, Maubant, S, Luis, J, Gauduchon, P, Staedel, C, Dedhar, S 2003Alpha(v) integrins regulate cell proliferation through integrin-linked kinase (ILK) in ovarian cancer cellsOncogene2216881702Google Scholar
  16. Davidson, B, Goldberg, I, Reich, R, Tell, L, Dong, HP, Trope, CG, Risberg, B, Kopolovic, J 2003AlphaV- and beta 1-integrin subunits are commonly expressed in malignant effusions from ovarian carcinoma patientsGynecol Oncol90248257Google Scholar
  17. Gladson, CL, Cheresh, DA 1994The αv Integrins. Integrins the Biological ProblemsCRC PressBoca Raton8399Google Scholar
  18. Goldberg, I, Davidson, B, Reich, R, Gotlieb, WH, Ben-Baruch, G, Bryne, M, Berner, A, Nesland, JM, Kopolovic, J 2001Alphav integrin expression is a novel marker of poor prognosis in advanced-stage ovarian carcinomaClin Cancer Res740734079Google Scholar
  19. Hapke, S, Kessler, H, Luber, B, Benge, A, Hutzler, P, Hofler, H, Schmitt, M, Reuning, U. 2003Ovarian cancer cell proliferation and motility is induced by engagement of integrin alpha(v) beta 3/Vitronectin interactionBiol Chem38410731083Google Scholar
  20. Hibbs, K, Skubitz, KM, Pambuccian, SE, Casey, RC, Burleson, KM, Oegema, TR,Jr, Thiele, JJ, Grindle, SM, Bliss, RL, Skubitz, AP 2004Differential gene expression in ovarian carcinoma: identification of potential biomarkersAm J Pathol165397414Google Scholar
  21. Hood, JD, Cheresh, DA 2002Role of integrins in cell invasion and migrationNat RevCancer291100Google Scholar
  22. Huang, X, Wu, J, Spong, S, Sheppard, D 1998The integrin alphavbeta6 is critical for keratinocyte migration on both its known ligand, fibronectin, and on vitronectinJ Cell Sci11121892195Google Scholar
  23. Hynes, RO 1992Integrins: versatility, modulation, and signaling in cell adhesionCell691125Google Scholar
  24. Hynes, RO 2002Integrins: bi-directional, allosteric signaling machinesCell110673687Google Scholar
  25. Jones, J, Watt, FM, Speight, PM 1997Changes in the expression of αv integrins in oral squamous carcinomaJ Oral Pathol Med266368Google Scholar
  26. Liapis, H, Adler, LM, Wick, MR, Rader, JS 1997Expression of αvβ3 integrin is less frequent in ovarian epithelial tumours of low malignant potential in contrast to ovarian carcinomaHum Pathol28443449Google Scholar
  27. Maubant, S, Cruet-Hennequart, S, Poulain, L, Carreiras, F, Sichel, F, Luis, J, Staedel, C, Gauduchon, P 2002Altered adhesion properties and alpha v integrin expression in a cisplatin-resistant human ovarian carcinoma cell lineInt J Cancer97186194Google Scholar
  28. Muller-Klingspor, V, Hefler, L, Obermair, A, Kaider, A, Breitenecker, G, Leodolte, S, Kohlberger, P 2001Prognostic value of beta 1-integrin (CD29) in serous adenocarcinomas of the ovaryAnticancer Res2121852188Google Scholar
  29. Pasqualini, R, Bodorova, J, Ye, S, Hemler, ME 1993A study of the structure, function and distribution of β5 integrins using novel anti-β5 monoclonal antibodiesJ Cell Sci105101111Google Scholar
  30. Pignatelli, M, Stamp, G 1995Integrins in tumour development and spreadCancer Survey24113127Google Scholar
  31. Ramos, DM, Chen, BL, Boylen, K, Stern, M, Kramer, RH, Sheppard, D, Nishimura, SL, Greenspan, D, Zardi, L, Pytela, R 1997Stromal fibroblasts influence oral squamous-cell carcinoma cell interactions with tenascin-CInt J Cancer72369376Google Scholar
  32. Rothman, KJ, Boice, JD 1982Epidemiologic Analysis with a Programmable CalculatorEpidemiology Resources IncBostonGoogle Scholar
  33. Sethi, T, Rintoul, RC, Moore, SM, MacKinnon, AC, Salter, D, Choo, C, Chilvers, ER, Dransfield, I, Donnelly, SC, Strieter, R, Haslett, C 1999Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivoNat Med5662668Google Scholar
  34. Schwartz, MA, Ginsberg, MH 2002Networks and cross-talks: integrin signalling spreadsNat Cell Biol4E6568Google Scholar
  35. Skubitz, AP, Bast, RC Jr, Wayner, EA, Letourneau, PC, Wilke, MS 1996Expression of alpha 6 and beta 4 integrins in serous ovarian carcinoma correlates with expression of the basement membrane protein lamininAm J Pathol14814451461Google Scholar
  36. Smith, JW, Vestal, DJ, Irwin, SV, Burke, TA, Cheresh, DA 1990Purification and functional characterization of integrin alpha v beta 5. An adhesion receptor for vitronectinJ Biol Chem.2651100811013Google Scholar
  37. Strobel, T, Cannistra, SA 1999Beta-1 integrins partly mediate binding of ovarian cancer cells to peritoneal mesothelium in vitroGynecol Oncol73362367Google Scholar
  38. Uhm, JH, Dooley, NP, Kyritsis, AP, Rao, JS, Gladson, CL 1999Vitronectin, a glioma-derived extracellular matrix protein. protects tumour cells from apoptotic deathClin Cancer Res515871594Google Scholar
  39. Varner, JA, Cheresh, DA 1996Integrins and cancerCurr Opin Cell Biol8724730Google Scholar
  40. Vogel, BE, Tarone, G, Giancotti, FG, Gailit, J, Ruoslahti, E 1990A novel fibronectin receptor with an unexpected subunit composition (αvβ1)J Biol Chem26559345937Google Scholar
  41. Weinacker, A, Chen, A, Agrez, M, Cone, RI, Nishimura, S, Wayner, E, Pytela, R, Sheppard, D 1994Role of the integrin alpha v beta 6 in cell attachment to fibronectin. Heterologous expression of intact and secreted forms of the receptorJ Biol Chem26969406948Google Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Sylvie Maubant
    • 1
    • 5
  • Séverine Cruet-Hennequart
    • 1
    • 5
  • Soizic Dutoit
    • 1
    • 5
  • Yves Denoux
    • 2
    • 5
  • Hubert Crouet
    • 3
    • 5
  • Michel Henry-Amar
    • 4
    • 5
  • Pascal Gauduchon
    • 1
    • 5
  1. 1.Laboratoire de Cancérologie ExpérimentaleCentre de Lutte Contre le Cancer François BaclesseCaenFrance
  2. 2.Laboratoire d’Anatomie pathologiqueCentre de Lutte Contre le Cancer François BaclesseCaenFrance
  3. 3.Service de ChirurgieCentre de Lutte Contre le Cancer François BaclesseCaenFrance
  4. 4.Service de Recherche cliniqueCentre de Lutte Contre le Cancer François BaclesseCaenFrance
  5. 5.Groupe Régional d’Etudes sur le CancerUniversité de Caen-Basse NormandieCaenFrance

Personalised recommendations