Skip to main content

Advertisement

SpringerLink
Log in

Detection of Bone Sialoprotein in Human (Pre)neoplastic Lesions of the Uterine Cervix

  • Clinical Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Bone sialoprotein (BSP) is a secreted glycoprotein primarily found in the mineral compartment of developing bones. BSP is detected in a variety of human cancers, particularly those that metastasize to the skeleton. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone metastases development. Since squamous cell carcinoma (SCCs) of the uterine cervix also frequently metastasizes to bone, we investigated whether BSP is expressed in human cervical cancer. We examined BSP expression in cervical tissue samples from 47 patients, including 19 normal tissues, 20 squamous intraepithelial lesions (SILs) (9 low and 11 high grade) and 8 invasive SCCs. BSP protein expression was evaluated by the immunophosphatase technique using a BSP polyclonal antibody in paraffin-embedded cervical biopsies. The abundance of BSP protein was significantly higher in invasive SCCs and high grade SILs than in normal cervix tissue samples and low grade SILs, which showed no or a low level of anti-BSP immunoreactivity. In situ hybridization experiments performed on representative cervix invasive SCCs frozen sections revealed that BSP transcripts were detectable in these lesions. Our study demonstrates that BSP expression is a common feature in high grade SILs and invasive SCCs of the uterine cervix. The prognostic value of BSP detection in these lesions and the potential role of BSP as an angiogenic factor in this type of cancer are currently under investigation.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2

Similar content being viewed by others

References

  1. LW Fisher SW Whitson LV Avioli JD Termine (1983) ArticleTitleMatrix sialoprotein of developing bone. J Biol Chem 258 12723–12727 Occurrence Handle1:CAS:528:DyaL3sXlvFSisbY%3D Occurrence Handle6355090

    CAS  PubMed  Google Scholar 

  2. P Bianco LW Fisher MF Young JD Termine PG Robey (1991) ArticleTitleExpression of bone sialoprotein (BSP) in developing human tissues. Calcif Tissue Int 49 421–426 Occurrence Handle1:CAS:528:DyaK38Xht1Gms7s%3D Occurrence Handle1818768

    CAS  PubMed  Google Scholar 

  3. A Bellahcène MP Merville V Castronovo (1994) ArticleTitleExpression of bone sialoprotein, a bone matrix protein, in human breast cancer. Cancer Res 54 2823–2826 Occurrence Handle8187059

    PubMed  Google Scholar 

  4. A Bellahcène M Kroll F Liebens V Castronovo (1996) ArticleTitleBone sialoprotein expression in primary human breast cancer is associated with bone metastases development. J Bone Miner Res 11 665–670 Occurrence Handle9157781

    PubMed  Google Scholar 

  5. A Bellahcène N Antoine N Clausse E Tagliabue LW Fisher JM Kerr P Jares V Castronovo (1996) ArticleTitleDetection of bone sialoprotein in human breast cancer tissue and cell lines at both protein and messenger ribonucleic acid levels. Lab Invest 75 203–210 Occurrence Handle8765320

    PubMed  Google Scholar 

  6. A Bellahcène N Maloujahmoum LW Fisher H Pastorino E Tagliabue S Menard V Castronovo (1997) ArticleTitleExpression of bone sialoprotein in human lung cancer. Calcif Tissue Int 61 183–188 Occurrence Handle10.1007/s002239900320 Occurrence Handle9262507

    Article  PubMed  Google Scholar 

  7. A Bellahcène V Albert L Pollina F Basolo LW Fisher V Castronovo (1998) ArticleTitleEctopic expression of bone sialoprotein in human thyroid cancer. Thyroid 8 637–641 Occurrence Handle9737356

    PubMed  Google Scholar 

  8. D Waltregny A Bellahcène I Van Riet LW Fisher M Young P Fernandez W Dewe J de Leval V Castronovo (1998) ArticleTitlePrognostic value of bone sialoprotein expression in clinically localized human prostate cancer. J Natl Cancer Inst 90 1000–1008 Occurrence Handle10.1093/jnci/90.13.1000 Occurrence Handle1:CAS:528:DyaK1cXksVSnsbk%3D Occurrence Handle9665149

    Article  CAS  PubMed  Google Scholar 

  9. G De Pinieux T Flam M Zerbib P Taupin A Bellahcène D Waltregny A Vieillefond MF Poupon (2001) ArticleTitleBone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression in localized human prostatic adenocarcinoma as predictors of clinical outcome: a clinicopathological and immunohistochemical study of 43 cases. J Urol 166 1924–1930 Occurrence Handle1:CAS:528:DC%2BD3MXotVWls78%3D Occurrence Handle11586262

    CAS  PubMed  Google Scholar 

  10. A Bellahcène S Menard R Bufalino L Moreau V Castronovo (1996) ArticleTitleExpression of bone sialoprotein in primary human breast cancer is associated with poor survival. Int J Cancer 69 350–353 Occurrence Handle10.1002/(SICI)1097-0215(19960822)69:4<350::AID-IJC19>3.3.CO;2-P Occurrence Handle8797881

    Article  PubMed  Google Scholar 

  11. A Bellahcène K Bonjean B Fohr NS Fedarko FA Robey MF Young LW Fisher V Castronovo (2000) ArticleTitleBone sialoprotein mediates human endothelial cell attachment and migration and promotes angiogenesis. Circ Res 86 885–891 Occurrence Handle1:CAS:528:DC%2BD3cXjtVehtbY%3D Occurrence Handle10785511

    CAS  PubMed  Google Scholar 

  12. JM Walboomers MV Jacobs MM Manos FX Bosch JA Kummer KV Shah PJ Snijders J Peto CJ Meijer N Munoz (1999) ArticleTitleHuman papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189 12–19 Occurrence Handle1:STN:280:DyaK1Mzot1CjsQ%3D%3D Occurrence Handle10451482

    CAS  PubMed  Google Scholar 

  13. RY Kim B Weppelmann MM Salter DJ Brascho (1987) ArticleTitleSkeletal metastases from cancer of the uterine cervix: frequency, patterns, and radiotherapeutic significance. Int J Radiat Oncol Biol Phys 13 705–708 Occurrence Handle1:STN:280:BiiC1MvhtFY%3D Occurrence Handle3553112

    CAS  PubMed  Google Scholar 

  14. BL Baid L Kumar S Chander GK Rath S Kumar A Kriplani N Batla (1992) ArticleTitleBone metastases in the patients of carcinoma cervix. Indian J Cancer 29 71–75 Occurrence Handle1:STN:280:ByyC3MvnvF0%3D Occurrence Handle1473836

    CAS  PubMed  Google Scholar 

  15. T Matsuyama N Tsukamoto M Imachi H Nakano (1989) ArticleTitleBone metastasis from cervix cancer. Gynecol Oncol 32 72–75 Occurrence Handle1:STN:280:BiaD2sbgvFQ%3D Occurrence Handle2909450

    CAS  PubMed  Google Scholar 

  16. H Fagundes CA Perez PW Grigsby MA Lockett (1992) ArticleTitleDistant metastases after irradiation alone in carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 24 197–204 Occurrence Handle1:STN:280:By2H3cnls1E%3D Occurrence Handle1526855

    CAS  PubMed  Google Scholar 

  17. E Barmeir O Langer JI Levy M Nissenbaum NG DeMoor NJ Blumenthal (1985) ArticleTitleUnusual skeletal metastases in carcinoma of the cervix. Gynecol Oncol 20 307–316 Occurrence Handle1:STN:280:BiqC38fmt1I%3D Occurrence Handle3972292

    CAS  PubMed  Google Scholar 

  18. P Delvenne WJ Engellenner SF Ma WJ Mann E Chalas GJ Nuovo (1992) ArticleTitleDetection of human papillomavirus DNA in biopsy-proven cervical squamous intraepithelial lesions in pregnant women. J Reprod Med 37 829–833 Occurrence Handle1:STN:280:ByyC38vkt10%3D Occurrence Handle1336051

    CAS  PubMed  Google Scholar 

  19. P Delvenne MA Fontaine C Delvenne A Nikkels J Boniver (1994) ArticleTitleDetection of human papillomaviruses in paraffin-embedded biopsies of cervical intraepithelial lesions: analysis by immunohistochemistry, in situ hybridization, and the polymerase chain reaction. Mod Pathol 7 113–119 Occurrence Handle1:STN:280:ByuB3M7nt1E%3D Occurrence Handle8159640

    CAS  PubMed  Google Scholar 

  20. GJ Nuovo MM Darfler CC Impraim SE Bromley (1991) ArticleTitleOccurrence of multiple types of human papillomavirus in genital tract lesions. Analysis by in situ hybridization and the polymerase chain reaction. Am J Pathol 138 53–58 Occurrence Handle1:STN:280:By6C3czis1c%3D Occurrence Handle1846265

    CAS  PubMed  Google Scholar 

  21. GJ Nuovo P Delvenne P MacConnell E Chalas C Neto WJ Mann (1991) ArticleTitleCorrelation of histology and detection of human papillomavirus DNA in vulvar cancers. Gynecol Oncol 43 275–280 Occurrence Handle1:STN:280:By2D1M%2FnvF0%3D Occurrence Handle1661264

    CAS  PubMed  Google Scholar 

  22. MH Schiffman HM Bauer AT Lorincz MM Manos JC Byrne AG Glass DM Cadell PM Howley (1991) ArticleTitleComparison of Southern blot hybridization and polymerase chain reaction methods for the detection of human papillomavirus DNA. J Clin Microbiol 29 573–577 Occurrence Handle1:CAS:528:DyaK3MXltlSqsbg%3D Occurrence Handle1645370

    CAS  PubMed  Google Scholar 

  23. KP Mintz WJ Grzesik RJ Midura PG Robey JD Termine LW Fisher (1993) ArticleTitlePurification and fragmentation of nondenatured bone sialoprotien: evidence for a cryptic, RGD-resistant cell attachment domain. J Bone Miner Res 8 985–995 Occurrence Handle1:CAS:528:DyaK2cXlvFykt7w%3D Occurrence Handle8213261

    CAS  PubMed  Google Scholar 

  24. LW Fisher OW McBride JD Termine MF Young (1990) ArticleTitleHuman bone sialoprotein. Deduced protein sequence and chromosomal localization. J Biol Chem 265 2347–2351 Occurrence Handle1:CAS:528:DyaK3cXkslait7w%3D Occurrence Handle2404984

    CAS  PubMed  Google Scholar 

  25. DM Parkin E Laara CS Muir (1988) ArticleTitleEstimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer 41 184–197 Occurrence Handle1:STN:280:BieC3MvhsFA%3D Occurrence Handle3338870

    CAS  PubMed  Google Scholar 

  26. FX Bosch MM Manos N Munoz M Sherman AM Jansen J Peto MH Schiffman V Moreno R Kurman KV Shah (1995) ArticleTitlePrevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 87 796–802 Occurrence Handle1:STN:280:ByqA3M7jt1w%3D Occurrence Handle7791229

    CAS  PubMed  Google Scholar 

  27. MF Cox CA Meanwell NJ Maitland G Blackledge C Scully JA Jordan (1986) ArticleTitleHuman papillomavirus type-16 homologous DNA in normal human ectocervix. Lancet 2 157–158 Occurrence Handle10.1016/S0140-6736(86)91965-3 Occurrence Handle1:STN:280:BimB2MngtVQ%3D Occurrence Handle2873415

    Article  CAS  PubMed  Google Scholar 

  28. PG Toon JR Arrand LP Wilson DS Sharp (1986) ArticleTitleHuman papillomavirus infection of the uterine cervix of women without cytological signs of neoplasia. Br Med J (Clin Res Ed) 293 1261–1264 Occurrence Handle1:STN:280:BiiD2M%2Fms1I%3D

    CAS  Google Scholar 

  29. MP Hopkins GW Morley (1993) ArticleTitlePrognostic factors in advanced stage squamous cell cancer of the cervix. Cancer 72 2389–2393 Occurrence Handle1:STN:280:ByuD3cngsVA%3D Occurrence Handle8402454

    CAS  PubMed  Google Scholar 

  30. FW Abdul-Karim M Kida WB Wentz JR Carter K Sorensen M Macfee J Zika JT Makley (1990) ArticleTitleBone metastasis from gynecologic carcinomas: a clinicopathologic study. Gynecol Oncol 39 108–114 Occurrence Handle1:STN:280:By6D3szisVA%3D Occurrence Handle2227582

    CAS  PubMed  Google Scholar 

  31. A Bellahcène D Waltregny V Castronovo (1999) The role of bone sialoprotein in the process of bone metastases development. GG Skouteris GL Nicolson (Eds) Intermolecular cross-talk in tumor metastasis. IOS Press Amsterdam 67–77

    Google Scholar 

  32. IJ Diel EF Solomayer MJ Seibel J Pfeilschifter H Maisenbacher C Gollan M Pecherstorfer R Conradi G Kehr E Boehm FP Armbruster G Bastert (1999) ArticleTitleSerum bone sialoprotein in patients with primary breast cancer is a prognostic marker for subsequent bone metastasis. Clin Cancer Res 5 3914–3919 Occurrence Handle1:STN:280:DC%2BD3c%2Fps1Wrsw%3D%3D Occurrence Handle10632320

    CAS  PubMed  Google Scholar 

  33. HW Woitge M Pecherstorfer E Horn AV Keck IJ Diel P Bayer H Ludwig R Ziegler MJ Seibel (2001) ArticleTitleSerum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma. Br J Cancer 84 344–351 Occurrence Handle10.1054/bjoc.2000.1614 Occurrence Handle1:CAS:528:DC%2BD3MXitFCitL0%3D Occurrence Handle11161399

    Article  CAS  PubMed  Google Scholar 

  34. D Waltregny A Bellahcene X de Leval B Florkin U Weidle V Castronovo (2000) ArticleTitleIncreased expression of bone sialoprotein in bone metastases compared with visceral metastases in human breast and prostate cancers. J Bone Miner Res 15 834–843 Occurrence Handle1:CAS:528:DC%2BD3cXjt1Crs78%3D Occurrence Handle10804012

    CAS  PubMed  Google Scholar 

  35. O Abulafia DM Sherer (2000) ArticleTitleAngiogenesis in the uterine cervix. Int J Gynecol Cancer 10 349–357 Occurrence Handle10.1046/j.1525-1438.2000.010005349.x Occurrence Handle11240698

    Article  PubMed  Google Scholar 

  36. KK Smith-McCune N Weidner (1994) ArticleTitleDemonstration and characterization of the angiogenic properties of cervical dysplasia. Cancer Res 54 800–804 Occurrence Handle1:STN:280:ByuC3sfpsVA%3D Occurrence Handle7508337

    CAS  PubMed  Google Scholar 

  37. N Chattopadhyay A Chatterjee (2001) ArticleTitleStudies on the expression of alpha(v)beta3 integrin receptors in non-malignant and malignant human cervical tumor tissues. J Exp Clin Cancer Res 20 269–275 Occurrence Handle1:CAS:528:DC%2BD3MXlslGrsLk%3D Occurrence Handle11484986

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Pr. J. Boniver (Head of the Pathology Department, University of Liege) for providing the biopsy material and Mrs. P. Heneaux for excellent technical assistance. We are grateful to Dr. L.W. Fisher (Craniofacial and Skeletal Diseases Branch, National Institute of Dental Research, National Institutes of Health, MD, USA) for kindly providing us with the antibodies. P. Delvenne is a Senior Research Associate, A. Bellahcène and D. Waltregny are Research Associates and C. Detry is a Télévie Research Fellow of the Belgian Fund for Scientific Research.

Author information

Authors and Affiliations

  1. Metastasis Research Laboratory, Center of Experimental Cancer Research, University of Liège, Belgium

    C. Detry, D. Waltregny, M. Chaplet, V. Castronovo & A. Bellahcène

  2. Department of Pathology, Center of Experimental Cancer Research, University of Liège, Belgium

    P. Quatresooz & P. Delvenne

  3. Department of Gynecology and Obstetrics, Karol Marcinkowski School of Medicine, Poznan, Poland

    W. Kedzia

Authors
  1. C. Detry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Waltregny
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Quatresooz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Chaplet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W. Kedzia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. Castronovo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Delvenne
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Bellahcène
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Bellahcène.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Detry, C., Waltregny, D., Quatresooz, P. et al. Detection of Bone Sialoprotein in Human (Pre)neoplastic Lesions of the Uterine Cervix . Calcif Tissue Int 73, 9–14 (2003). https://doi.org/10.1007/s00223-002-2108-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-002-2108-0

Keywords

Search

Navigation