[en] Recent studies have demonstrated that two SIBLING family members, bone sialoprotein (BSP) and osteopontin (OPN), are overexpressed in human prostate cancer. The expression of these proteins is associated with the acquisition of a metastatic phenotype by cancer cells and a poor prognosis for the patient. Dentin sialophosphoprotein (DSPP) shares several structural and genetic features with OPN and BSP. The presence of DSPP has been recently established in salivary glands, indicating that its expression is not restricted to mineralized tissues. However, its potential expression in human tumors has not been addressed yet. In this study, we sought to evaluate the expression of DSPP in human prostate cancer. Immunohistochemistry was performed on 69 prostate cancer specimens using LFMb-21 anti-DSPP monoclonal antibody. All of the prostate cancer lesions examined expressed detectable levels of DSPP, as compared with no or low level of expression in adjacent normal glands (p < 0.0001). High grade prostatic intraepithelial neoplasia (HGPIN) glands generally displayed DSPP expression levels that were similar to those found in neighboring cancer glands. DSPP expression was significantly associated with the pathological stage (p = 0.0087) and the Gleason score (p = 0.0176) of the tumors. Western Blot was performed on 5 representative prostate tumor extracts and 3 prostatic tumor cell lines (PC3, LNCaP and DU145). All tumor extracts and cell lines analyzed have been found to express DSPP. In addition, in situ hybridization was used to assess the presence of DSPP mRNA. DSPP was detected at the RNA level in both HGPIN and tumoral glands. This study shows for the first time that DSPP is ectopically expressed in human prostate cancer. The expression of this SIBLING protein strongly correlates with conventional histopathological prognostic indicators of prostate cancer progression. (c) 2005 Wiley-Liss, Inc.
Disciplines :
Oncology
Author, co-author :
Chaplet, Michael
Waltregny, David ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases
Detry, Cédric ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Service administratif de la Faculté (Médecine)
Fisher, Larry
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Labo de recherche sur les métastases
Language :
English
Title :
Expression of dentin sialophosphoprotein in human prostate cancer and its correlation with tumor aggressiveness
Publication date :
February 2006
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., Hoboken, United States - New Jersey
Fisher LW, Torchia DA, Fohr B, Young MF, Fedarko NS. Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin. Biochem Biophys Res Commun 2001;280:460-5.
Bellahcène A, Merville MP, Castronovo V. Expression of bone sialoprotein, a bone matrix protein, in human breast cancer. Cancer Res 1994;54:2823-6.
Bellahcène A, Castronovo V. Increased expression of osteonectin and osteopontin, two bone matrix proteins, in human breast cancer. Am J Pathol 1995;146:95-100.
Brown LF, Papadopoulos-Sergiou A, Berse B, Manseau EJ, Tognazzi K, Perruzzi CA, Dvorak HF, Senger DR. Osteopontin expression and distribution in human carcinomas. Am J Pathol 1994;145: 610-23.
Waltregny D, Bellahcene A, Van Riet I, Fisher LW, Young M, Fernandez P, Dewe W, de Leval J, Castronovo V. Prognostic value of bone sialoprotein expression in clinically localized human prostate cancer. J Natl Cancer Inst 1998;90:1000-8.
Chambers AF, Wilson SM, Kerkvliet N, O'Malley FP, Harris JF, Casson AG. Osteopontin expression in lung cancer. Lung Cancer 1996; 15:311-23.
Bellahcène A, Maloujahmoum N, Fisher LW, Pastorino H, Tagliabue E, Menard S, Castronovo V. Expression of bone sialoprotein in human lung cancer. Calcif Tissue Int 1997;61:183-8.
Chaplet M, De Leval L, Waltregny D, Detry C, Fornaciari G, Bevilacqua G, Fisher LW, Castronovo V, Bellahcene A. Dentin matrix protein 1 is expressed in human lung cancer. J Bone Miner Res 2003;18:1506-12.
Bellahcène A, Kroll M, Liebens F, Castronovo V. Bone sialoprotein expression in primary human breast cancer is associated with bone metastases development. J Bone Miner Res 1996;11:665-70.
Bellahcène A, Menard S, Bufalino R, Moreau L, Castronovo V. Expression of bone sialoprotein in primary human breast cancer is associated with poor survival. Int J Cancer 1996;69:350-3.
Thalmann GN, Sikes RA, Devoll RE, Kiefer JA, Markwalder R, Klima I, Farach-Carson CM, Studer UE, Chung LW. Osteopontin: possible role in prostate cancer progression. Clin Cancer Res 1999;5: 2271-7.
Waltregny D, Bellahcene A, de Levai X, Florkin B, Weidle U, Castronovo V. Increased expression of bone sialoprotein in bone metastases compared with visceral metastases in human breast and prostate cancers. J Bone Miner Res 2000;15:834-43.
Rudland PS, Platt-Higgins A, El-Tanani M, De Silva Rudland S, Barraclough R, Winstanley JH, Howitt R, West CR. Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res 2002;62:3417-27.
Rowe PS, de Zoysa PA, Dong R, Wang HR, White KE, Econs MJ, Oudet CL. MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia. Genomics 2000;67:54-68.
Linde A, Goldberg M. Dentinogenesis. Crit Rev Oral Biol Med 1993;4:679-728.
Qin C, Brunn JC, Cadena E, Ridall A, Tsujigiwa H, Nagatsuka H, Nagai N, Butler WT. The expression of dentin sialophosphoprotein gene in bone. J Dent Res 2002;81:392-4.
Qin C, Brunn JC, Cadena E, Ridall A, Butler WT. Dentin sialoprotein in bone and dentin sialophosphoprotein gene expressed by osteoblasts. Connect Tissue Res 2003;44 (Suppl 1):179-83.
Feng JQ, Luan X, Wallace J, Jing D, Ohshima T, Kulkarni AB, D'Souza RN, Kozak CA, MacDougall M. Genomic organization, chromosomal mapping, and promoter analysis of the mouse dentin sialophosphoprotein (Dspp) gene, which codes for both dentin sialoprotein and dentin phosphoprotein. J Biol Chem 1998;273:9457-64.
Butler WT, Brunn JC, Qin C, McKee MD. Extracellular matrix proteins and the dynamics of dentin formation. Connect Tissue Res 2002;43:301-7.
Qin C, Baba O, Butler WT. Post-translational modifications of sibling proteins and their roles in osteogenesis and dentinogenesis. Crit Rev Oral Biol Med 2004;15:126-36.
Ogbureke K, Fisher L. Expression of SIBLINGS and their partner MMPs in salivary glands. J Dent Res 2004;83:664-70.
Fedarko NS, Jain A, Karadag A, Fisher LW. Three small integrin binding ligand N-linked glycoproteins (SIBLINGS) bind and activate specific matrix metalloproteinases. Faseb J 2004;18:734-6.
Karadag A, Ogbureke KU, Fedarko NS, Fisher LW. Bone sialoprotein, matrix metalloproteinase 2, and alpha(v)beta3 integrin in osteotropic cancer cell invasion. J Natl Cancer Inst 2004;96:956-65.
Schroder FH, Hermanek P, Denis L, Fair WR, Gospodarowicz MK, Pavone-Macaluso M. The TNM classification of prostate cancer. Prostate Suppl 1992;4:129-38.
Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 1974;111:58-64.
Goldberg HA, Warner KJ. The staining of acidic proteins on polyacrylamide gels; enhanced sensitivity and stability of "Stains-all" staining in combination with silver nitrate. Anal Biochem 1997;251: 227-33.
Koeneman KS, Yeung F, Chung LW. Osteomimetic properties of prostate cancer cells: a hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment. Prostate 1999;39:246-61.
Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, Pathak S, von Eschenbach AC, Chung LW. Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 1994;54;2577-81.
Lin DL, Tarnowski CP, Zhang J, Dai J, Rohn E, Patel AH, Morris MD, Keller ET. Bone metastatic LNCaP-derivative C4-2B prostate cancer cell line mineralizes in vitro. Prostate 2001;47;212-21.
DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI. Pathological and molecular aspects of prostate cancer. Lancet 2003;361:955-64.
Singhal H, Bautista DS, Tonkin KS, O'Malley FP, Tuck AB, Chambers AF, Harris JF. Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival. Clin Cancer Res 1997;3:605-11.
Fedarko NS, Jain A, Karadag A, Van Eman MR, Fisher LW. Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. Clin Cancer Res 2001;7:4060-6.
Diel IJ, Solomayer EF, Seibel MJ, Pfeilschifter J, Maisenbacher H, Gollan C, Pecherstorfer M, Conradi R, Kehr G, Boehm E, Armbruster FP, Basten G. Serum bone sialoprotein in patients with primary breast cancer is a prognostic marker for subsequent bone metastasis. Clin Cancer Res 1999;5:3914-9.
Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997;89: 747-54.
Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 1997;89: 755-64.
Sato M, Morii E, Komori T, Kawahata H, Sugimoto M, Terai K, Shimizu H, Yasui T, Ogihara H, Yasui N, Ochi T, Kitamura Y, et al. Transcriptional regulation of osteopontin gene in vivo by PEBP2alphaA/CBFA1 and ETS1 in the skeletal tissues. Oncogene 1998;17: 1517-25.
Jimenez MJ, Balbin M, Lopez JM, Alvarez J, Komori T, Lopez-Otin C. Collagenase 3 is a target of Cbfa1, a transcription factor of the runt gene family involved in bone formation. Mol Cell Biol 1999;19: 4431-42.
Porte D, Tuckermann J, Becker M, Baumann B, Teurich S, Higgins T, Owen MJ, Schorpp-Kistner M, Angel P. Both AP-1 and Cbfa1-like factors are required for the induction of interstitial collagenase by parathyroid hormone. Oncogene 1999;18:667-78.
Chen S, Gu TT, Sreenath T, Kulkarni AB, Karsenty G, MacDougall M. Spatial expression of Cbfa1/Runx2 isoforms in teeth and characterization of binding sites in the DSPP gene. Connect Tissue Res 2002; 43:338-44.
Barnes GL, Javed A, Waller SM, Kamal MH, Hebert KE, Hassan MQ, Bellahcene A, Van Wijnen AJ, Young MF, Lian JB, Stein GS, Gerstenfeld LC. Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. Cancer Res 2003;63:2631-7.
Inman CK, Shore P. The osteoblast transcription factor Runx2 is expressed in mammary epithelial cells and mediates osteopontin expression. J Biol Chem 2003;278:48684-9.
