World Journal of Urology

, Volume 28, Issue 4, pp 465–471 | Cite as

Maspin modulates adhesion of bladder carcinoma cells to vascular endothelium

  • Eva Juengel
  • Wolf-Dietrich C. Beecken
  • Santhosh Mundiyanapurath
  • Tobias Engl
  • Dietger Jonas
  • Roman A. Blaheta
Original Article



Maspin belongs to the serpin family and has been shown to suppress tumor growth and metastasis in several tumor types. The role of maspin in bladder carcinoma has not been fully elucidated, and the object of this study was to investigate whether maspin contributes to bladder tumor adhesion to vascular endothelial cells (HUVEC).


Expression of maspin-coding mRNA was evaluated in a panel of bladder carcinoma cell lines. Maspin distribution in maspin mRNAhigh versus maspin mRNAlow cells was further analyzed by flow cytometry and confocal microscopy. Adhesion to HUVEC was measured in a coculture model and correlated with the surface-bound maspin.


Maspinhigh (RT-4, RT-112) cell lines strongly attached to HUVEC, whereas maspinlow (UMUC-3, MGH-U1) cell lines poorly adhered to HUVEC. Distinct cytoplasmic maspin accumulation and moderate surface-bound maspin was found in RT-4 cells. Blocking maspin surface receptors prevented tumor cell attachment to HUVEC, indicating that surface-bound maspin is responsible for triggering cell adhesion. PMA-triggered elevation of surface-bound maspin was accompanied by an enhanced adhesion capacity of RT-4 cells, compared to controls. Finally, exposing the bladder carcinoma cells to the differentiation-inducing agent valproic acid led to a surface-bound (but not cytoplasmic) maspin decrease, paralleled by a significant reduction in tumor cell binding to HUVEC.


Surface-bound maspin directly controls bladder carcinoma cell adhesion to the vascular wall. Blocking this process may prevent transendothelial migration and tumor cell dissemination. Therefore, therapeutic down-regulation of surface-bound maspin might become an option to prevent tumor spread into distant organs.


Adhesion Bladder carcinoma HUVEC Maspin Valproic acid 



We would like to thank Karen Nelson for critically reading the manuscript. This work was supported by the “Horst Müggenburg-Stiftung”.

Conflict of interest statement

The authors declare that they have no conflict of interest.


  1. 1.
    Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, Rafidi K, Seftor E, Sager R (1994) Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science 263:526–529CrossRefPubMedGoogle Scholar
  2. 2.
    Khalkhali-Ellis Z (2006) Maspin: the new frontier. Clin Cancer Res 12:7279–7283CrossRefPubMedGoogle Scholar
  3. 3.
    Joensuu KM, Leidenius MH, Andersson LC, Heikkilä PS (2009) High expression of maspin is associated with early tumor relapse in breast cancer. Hum Pathol 40:1143–1151CrossRefPubMedGoogle Scholar
  4. 4.
    Hall DC, Johnson-Pais TL, Grubbs B, Bernal R, Leach RJ, Padalecki SS (2008) Maspin reduces prostate cancer metastasis to bone. Urol Oncol 26:652–658PubMedGoogle Scholar
  5. 5.
    Yoshizawa K, Nozaki S, Okamune A, Kitahara H, Ohara T, Kato K, Kawashiri S, Yamamoto E (2009) Loss of maspin is a negative prognostic factor for invasion and metastasis in oral squamous cell carcinoma. J Oral Pathol Med 38:535–539CrossRefPubMedGoogle Scholar
  6. 6.
    Chua R, Setzer S, Govindarajan B, Sexton D, Cohen C, Arbiser JL (2009) Maspin expression, angiogenesis, prognostic parameters, and outcome in malignant melanoma. J Am Acad Dermatol 60:758–766CrossRefPubMedGoogle Scholar
  7. 7.
    Frey A, Soubani AO, Adam AK, Sheng S, Pass HI, Lonardo F (2009) Nuclear, compared with combined nuclear and cytoplasmic expression of maspin, is linked in lung adenocarcinoma to reduced VEGF-A levels and in Stage I, improved survival. Histopathology 54:590–597CrossRefPubMedGoogle Scholar
  8. 8.
    Zheng H, Tsuneyama K, Cheng C, Takahashi H, Cui Z, Murai Y, Nomoto K, Takano Y (2007) Maspin expression was involved in colorectal adenoma-adenocarcinoma sequence and liver metastasis of tumors. Anticancer Res 27:259–265PubMedGoogle Scholar
  9. 9.
    Klasa-Mazurkiewicz D, Narkiewicz J, Milczek T, Lipińska B, Emerich J (2009) Maspin overexpression correlates with positive response to primary chemotherapy in ovarian cancer patients. Gynecol Oncol 113:91–98CrossRefPubMedGoogle Scholar
  10. 10.
    Yu M, Zheng H, Tsuneyama K, Takahashi H, Nomoto K, Xu H, Takano Y (2007) Paradoxical expression of maspin in gastric carcinomas: correlation with carcinogenesis and progression. Hum Pathol 38:1248–1255CrossRefPubMedGoogle Scholar
  11. 11.
    Terashima M, Maesawa C, Oyama K, Ohtani S, Akiyama Y, Ogasawara S, Takagane A, Saito K, Masuda T, Kanzaki N, Matsuyama S, Hoshino Y, Kogure M, Gotoh M, Shirane M, Mori K (2005) Gene expression profiles in human gastric cancer: expression of maspin correlates with lymph node metastasis. Br J Cancer 92:1130–1136CrossRefPubMedGoogle Scholar
  12. 12.
    Beecken WD, Engl T, Engels K, Blumenberg C, Oppermann E, Camphausen K, Shing Y, Reinecke G, Jonas D, Blaheta R (2006) Clinical relevance of maspin expression in bladder cancer. World J Urol 24:338–344CrossRefPubMedGoogle Scholar
  13. 13.
    Bal N, Kocer NE, Ertorer ME, Canpolat ET, Kayaselcuk F (2008) Maspin, E-selectin, and P-selectin expressions in papillary thyroid carcinomas and their correlation with prognostic parameters. Pathol Res Pract 204:743–750CrossRefPubMedGoogle Scholar
  14. 14.
    Cella N, Contreras A, Latha K, Rosen JM, Zhang M (2006) Maspin is physically associated with [beta]1 integrin regulating cell adhesion in mammary epithelial cells. FASEB J 20:1510–1512CrossRefPubMedGoogle Scholar
  15. 15.
    Ngamkitidechakul C, Warejcka DJ, Burke JM, O’Brien WJ, Twining SS (2003) Sufficiency of the reactive site loop of maspin for induction of cell-matrix adhesion and inhibition of cell invasion. Conversion of ovalbumin to a maspin-like molecule. J Biol Chem 278:31796–31806CrossRefPubMedGoogle Scholar
  16. 16.
    Abraham S, Zhang W, Greenberg N, Zhang M (2003) Maspin functions as tumor suppressor by increasing cell adhesion to extracellular matrix in prostate tumor cells. J Urol 169:1157–1161CrossRefPubMedGoogle Scholar
  17. 17.
    Blacque OE, Worrall DM (2002) Evidence for a direct interaction between the tumor suppressor serpin, maspin, and types I and III collagen. J Biol Chem 277:10783–10788CrossRefPubMedGoogle Scholar
  18. 18.
    Gan L, Chen S, Wang Y, Watahiki A, Bohrer L, Sun Z, Wang Y, Huang H (2009) Inhibition of the androgen receptor as a novel mechanism of taxol chemotherapy in prostate cancer. Cancer Res 69:8386–8394CrossRefPubMedGoogle Scholar
  19. 19.
    McKenzie S, Sakamoto S, Kyprianou N (2008) Maspin modulates prostate cancer cell apoptotic and angiogenic response to hypoxia via targeting AKT. Oncogene 27:7171–7179CrossRefPubMedGoogle Scholar
  20. 20.
    Blandamura S, D’Alessandro E, Giacomelli L, Guzzardo V, Battanello W, Repele M, Ninfo V (2008) Expression of maspin in papillary Ta/T1 bladder neoplasms. Anticancer Res 28:471–478PubMedGoogle Scholar
  21. 21.
    Friedrich MG, Toma MI, Petri S, Cheng JC, Hammerer P, Erbersdobler A, Huland H (2004) Expression of maspin in non-muscle invasive bladder carcinoma: correlation with tumor angiogenesis and prognosis. Eur Urol 45:737–743CrossRefPubMedGoogle Scholar
  22. 22.
    Sugimoto S, Maass N, Takimoto Y, Sato K, Minei S, Zhang M, Hoshikawa Y, Jünemann KP, Jonat W, Nagasaki K (2004) Expression and regulation of tumor suppressor gene maspin in human bladder cancer. Cancer Lett 203:209–215CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Eva Juengel
    • 1
  • Wolf-Dietrich C. Beecken
    • 1
  • Santhosh Mundiyanapurath
    • 1
  • Tobias Engl
    • 1
  • Dietger Jonas
    • 1
  • Roman A. Blaheta
    • 1
  1. 1.Klinik für Urologie und Kinderurologie, Zentrum der ChirurgieJohann Wolfgang Goethe-UniversitätsklinikFrankfurt am MainGermany

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