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Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma

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Abstract

Breast and prostate cancer often metastasise to the skeleton. Interestingly, the histopathological characteristics of the bone lesions that arise from these two cancer types differ. Breast tumours give rise to metastases in the skeleton with a mixed lytic/sclerotic pattern, whereas a predominantly sclerotic pattern is seen in metastases from prostate tumours. Osteopontin (OPN) and bone sialoprotein (BSP) are bone matrix proteins that have been implicated in the selective affinity of cancer cells for bone. In the present study, 21 patient cases with skeletal metastasis and their respective primary tumours (12 with breast cancer, 9 with prostate cancer) were investigated by immunohistochemistry in order to assess the level of OPN and BSP. Moderate to strong OPN expression was found in 42% of all breast tumours and in 56% of all prostate tumours. Significantly more breast cancer bone metastases exhibited high OPN expression, 83%, as compared with prostate tumour bone metastases, 11% (P=0.0019). In contrast, moderate to strong BSP expression was found in 33% of breast tumours and in 89% of prostate tumours. In the bone lesions, only 33% of breast tumour metastases showed moderate/strong BSP expression compared to 100% of prostate tumour metastases (P=0.0046). This divergent pattern of OPN/BSP expression could be an important determinant for the different characteristics of these two types of bone metastasis, i.e., lytic vs. sclerotic, consistent with the proposed role of OPN in differentiation and activation of osteoclasts and of BSP as a stimulator of bone mineralisation.

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References

  1. Mundy GR. Mechanisms of bone metastasis. Cancer 1997; 80: 1546–56.

    Article  PubMed  CAS  Google Scholar 

  2. Giachelli CM, Steitz S. Osteopontin: A versatile regulator of inflammation and biomineralization. Matrix Biol 2000; 19: 615–22.

    Article  PubMed  CAS  Google Scholar 

  3. Sodek J, Ganss B, McKee MD. Osteopontin. Crit Rev Oral Biol Med 2000; 11: 279–303.

    Article  PubMed  CAS  Google Scholar 

  4. Heinegard D, Andersson G, Reinholt FP. Roles of osteopontin in bone remodeling. Ann NY Acad Sci 1995; 760: 213–22.

    PubMed  CAS  Google Scholar 

  5. Brown LF, Berse B, Van de Water L et al. Expression and distribution of osteopontin in human tissues: Widespread association with luminal epithelial surfaces. Mol Biol Cell 1992; 3: 1169–80.

    PubMed  CAS  Google Scholar 

  6. Oates AJ, Barraclough R, Rudland PS. The role of osteopontin in tumorigenesis and metastasis. Invasion Metastasis 1997; 17: 1–15.

    PubMed  CAS  Google Scholar 

  7. Singhal H, Bautista DS, Tonkin KS et al. Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival. Clin Cancer Res 1997; 3: 605–11.

    PubMed  CAS  Google Scholar 

  8. Sung V, Gilles C, Murray A et al. The LCC15—MB human breast cancer cell line expresses osteopontin and exhibits an invasive and metastatic phenotype. Exp Cell Res 1998; 241: 273–84.

    Article  PubMed  CAS  Google Scholar 

  9. Tuck AB, O'Malley FP, Singhal H et al. Osteopontin expression in a group of lymph node negative breast cancer patients. Internl J Cancer 1998; 79: 502–8.

    Article  CAS  Google Scholar 

  10. Oates AJ, Barraclough R, Rudland PS. The identification of osteopontin as a metastasis—related gene product in a rodent mammary tumour model. Oncogene 1996; 13: 97–104.

    PubMed  CAS  Google Scholar 

  11. Ihara H, Denhardt DT, Furuya K et al. Parathyroid hormone—induced bone resorption does not occur in the absence of osteopontin. J Biol Chem 2001; 276: 13065–71.

    Article  PubMed  CAS  Google Scholar 

  12. Ganss B, Kim RH, Sodek J. Bone sialoprotein. Crit Rev Oral Biol Med 1999; 10: 79–98.

    PubMed  CAS  Google Scholar 

  13. Duong LT, Rodan GA. Integrin—mediated signaling in the regulation of osteoclast adhesion and activation. Front Biosci 1998; 3: 757–68.

    Google Scholar 

  14. Ross FP, Chappel J, Alvarez JI et al. Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption. J Biol Chem 1993; 268: 9901–7.

    PubMed  CAS  Google Scholar 

  15. Diel IJ, Solomayer EF, Seibel MJ et al. Serum bone sialoprotein in patients with primary breast cancer is a prognostic marker for subsequent bone metastasis. Clin Cancer Res 1999; 5: 3914–9.

    PubMed  CAS  Google Scholar 

  16. Waltregny D, Bellahcene A, Van Riet I et al. Prognostic value of bone sialoprotein expression in clinically localized human prostate cancer. J Natl Cancer Inst 1998; 90: 1000–8.

    Article  PubMed  CAS  Google Scholar 

  17. Bellahcene A, Maloujahmoum N, Fisher LW et al. Expression of bone sialoprotein in human lung cancer. Calcif Tissue Int 1997; 61: 183–8.

    Article  PubMed  CAS  Google Scholar 

  18. Bellahcene A, Albert V, Pollina L et al. Ectopic expression of bone sialoprotein in human thyroid cancer. Thyroid 1998; 8: 637–41.

    Article  PubMed  CAS  Google Scholar 

  19. Bellahcene A, Van Riet I, de Greef C et al. Bone sialoprotein mRNA and protein expression in human multiple myeloma cell lines and patients. Br J Haematol 2000; 111: 1118–21.

    Article  PubMed  CAS  Google Scholar 

  20. Waltregny D, Bellahcene A, de Leval X et al. 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.

    Article  PubMed  CAS  Google Scholar 

  21. Fisher LW, Torchia DA, Fohr B et al. Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin. Biochem Biophys Res Commun 2001; 280: 460–5.

    Article  PubMed  CAS  Google Scholar 

  22. Senger DR, Perruzzi CA, Papadopoulos A et al. Purification of a human milk protein closely similar to tumor—secreted phosphoproteins and osteopontin. Biochim Biophys Acta 1989; 996: 43–8.

    PubMed  CAS  Google Scholar 

  23. Young MF, Kerr JM, Termine JD et al. cDNA cloning, mRNA distribution and heterogeneity, chromosomal location, and RFLP analysis of human osteopontin (OPN). Genomics 1990; 7: 491–502.

    Article  PubMed  CAS  Google Scholar 

  24. Bellahcene A, Bonjean K, Fohr B et al. Bone sialoprotein mediates human endothelial cell attachment and migration and promotes angiogenesis. Circ Res 2000; 86: 885–91.

    PubMed  CAS  Google Scholar 

  25. Rittling SR, Feng F. Detection of mouse osteopontin by Western blotting. Biochem Biophys Res Commun 1998; 250: 287–92.

    Article  PubMed  CAS  Google Scholar 

  26. Lang P, Schultzberg M, Andersson G. Expression and distribution of tartrate—resistant purple acid phosphatase in the rat nervous system. J Histochem Cytochem 2001; 49: 379–96.

    PubMed  CAS  Google Scholar 

  27. Fisher LW, Hawkins GR, Tuross N et al. Purification and partial characterization of small proteoglycans I and II, bone sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone. J Biol Chem 1987; 262: 9702–8.

    PubMed  CAS  Google Scholar 

  28. Mintz KP, Grzesik WJ, Midura RJ et al. Purification and fragmentation of nondenatured bone sialoprotein: Evidence for a cryptic, RGD—resistant cell attachment domain. J Bone Miner Res 1993; 8: 985–95.

    PubMed  CAS  Google Scholar 

  29. Fedarko NS, Fohr B, Robey PG et al. Factor H binding to bone sialoprotein and osteopontin enables tumor cell evasion of complement—mediated attack. J Biol Chem 2000; 275: 16666–72.

    Article  PubMed  CAS  Google Scholar 

  30. Qu H, Brown LF, Dvorak HF et al. Ultrastructural immunogold localization of osteopontin in human gastric mucosa. J Histochem Cytochem 1997; 45: 21–33.

    Google Scholar 

  31. Thalmann GN, Sikes RA, Devoll RE et al. Osteopontin: Possible role in prostate cancer progression. Clin Cancer Res 1999; 5: 2271–7.

    PubMed  CAS  Google Scholar 

  32. Paget S. The distribution of secondary growths in cancer of the breast. The Lancet 1889; 1: 571–2.

    Article  Google Scholar 

  33. Bellahcene A, Kroll M, Liebens F et al. Bone sialoprotein expression in primary human breast cancer is associated with bone metastases development. J Bone Min Res 1996; 11: 665–70.

    Article  CAS  Google Scholar 

  34. Lehr JE, Pienta KJ. Preferential adhesion of prostate cancer cells to a human bone marrow endothelial cell line [see comments]. J Natl Cancer Inst 1998; 90: 118–23.

    Article  PubMed  CAS  Google Scholar 

  35. Rittling SR, Novick KE. Osteopontin expression in mammary gland development and tumorigenesis. Cell Growth Differ 1997; 8: 1061–9.

    PubMed  CAS  Google Scholar 

  36. Tuck AB, O'Malley FP, Singhal H et al. Osteopontin and p53 expression are associated with tumor progression in a case of synchronous, bilateral, invasive mammary carcinomas. Arch Pathol Labo Med 1997; 121: 578–84.

    CAS  Google Scholar 

  37. Rudland PS, Platt—Higgins A, El—Tanani M et al. Prognostic significance of the metastasis—associated protein osteopontin in human breast cancer. Cancer Res 2002; 62: 3417–27.

    PubMed  CAS  Google Scholar 

  38. Bellahcene A, Merville MP, Castronovo V. Expression of bone sialoprotein, a bone matrix protein, in human breast cancer. Cancer Res 1994; 54: 2823–6.

    PubMed  CAS  Google Scholar 

  39. Bellahcene A, Castronovo V. Expression of bone matrix proteins in human breast cancer: Potential roles in microcalcification formation and in the genesis of bone metastases. Bull Cancer 1997; 84: 17–24.

    PubMed  CAS  Google Scholar 

  40. 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.

    Article  PubMed  CAS  Google Scholar 

  41. Sharp JA, Sung V, Slavin J et al. Tumor cells are the source of osteopontin and bone sialoprotein expression in human breast cancer. Lab Invest 1999; 79: 869–77.

    PubMed  CAS  Google Scholar 

  42. Hullinger TG, Taichman RS, Linseman DA et al. Secretory products from PC–3 and MCF–7 tumor cell lines upregulate osteopontin in MC3T3—E1 cells. J Cell Biochem 2000; 78: 607–16.

    Article  PubMed  CAS  Google Scholar 

  43. Ibrahim T, Leong I, Sanchez—Sweatman O et al. Expression of bone sialoprotein and osteopontin in breast cancer bone metastases. Clin Exp Metastasis 2000; 18: 253–60.

    Article  PubMed  CAS  Google Scholar 

  44. De Pinieux G, Flam T, Zerbib M et al. Bone 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 2001; 166: 1924–30.

    Article  PubMed  CAS  Google Scholar 

  45. Lin DL, Tarnowski CP, Zhang J et al. Bone metastatic LNCaP—derivative C4–2B prostate cancer cell line mineralizes in vitro. Prostate 2001; 47: 212–21.

    Article  PubMed  CAS  Google Scholar 

  46. Yang J, Fizazi K, Peleg S et al. Prostate cancer cells induce osteoblast differentiation through a Cbfa1—dependent pathway. Cancer Res 2001; 61: 5652–9.

    PubMed  CAS  Google Scholar 

  47. Liapis H, Flath A, Kitazawa S. Integrin alpha V beta 3 expression by bone—residing breast cancer metastases. Diagn Mol Pathol 1996; 5: 127–35.

    Article  PubMed  CAS  Google Scholar 

  48. Weber MH, Goltzman D, Kostenuik P et al. Mechanisms of tumor metastasis to bone. Crit Rev Eukaryot Gene Expr 2000; 10: 281–302.

    PubMed  CAS  Google Scholar 

  49. Orr FW, Lee J, Duivenvoorden WC et al. Pathophysiologic interactions in skeletal metastasis. Cancer 2000; 88: 2912–8.

    Article  PubMed  CAS  Google Scholar 

  50. Faid L, Van Riet I, De Waele M et al. Adhesive interactions between tumour cells and bone marrow stromal elements in human multiple myeloma. Europ J Haematol 1996; 57: 349–58.

    Article  CAS  Google Scholar 

  51. Chikatsu N, Takeuchi Y, Tamura Y et al. Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast—like cell formation in vitro. Biochem Biophys Res Commun 2000; 267: 632–7.

    Article  PubMed  CAS  Google Scholar 

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Author notes

  1. Gabriele Carlinfante

    Present address: Division of Pathology, Istituti Ospitalieridi Cremona, Cremona, Italy

  2. Olle Svensson

    Present address: Division of Orthopaedics, Umeá University, Umeá, Sweden

Authors and Affiliations

  1. Division of Pathology/ IMPI, Karolinska Institute, and Clinical Research Centre, Huddinge University Hospital, Huddinge, Sweden

    Gabriele Carlinfante & Göran Andersson

  2. Division of Pathology/ IMPI, Karolinska Institute, and Clinical Research Centre, Huddinge University Hospital, Huddinge, Sweden

    Daphne Vassiliou & Olle Svensson

  3. The Centre of Oral Biology, Novum Research Centre, Karolinska Institute, Huddinge, Sweden

    Mikael Wendel

  4. Department of Cell- and Molecular Biology, Lund University, Lund, Sweden

    Dick Heinegård

Authors
  1. Gabriele Carlinfante
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  2. Daphne Vassiliou
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Correspondence to Gabriele Carlinfante.

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Carlinfante, G., Vassiliou, D., Svensson, O. et al. Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma. Clin Exp Metastasis 20, 437–444 (2003). https://doi.org/10.1023/A:1025419708343

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