Clinical & Experimental Metastasis

, Volume 28, Issue 1, pp 65–73 | Cite as

Differential expression of tartrate-resistant acid phosphatase isoforms 5a and 5b by tumor and stromal cells in human metastatic bone disease

  • Serhan Zenger
  • Wentao He
  • Barbro Ek-Rylander
  • Daphne Vassiliou
  • Rickard Wedin
  • Henrik Bauer
  • Göran Andersson
Research Paper


Tartrate-resistant acid phosphatase (TRAP) exists in human serum as two major isoforms, monomeric 5a and proteolytically processed enzymatically active 5b. The 5b isoform is secreted by osteoclasts and has recently been advocated as a serum marker for bone metastasis in breast cancer patients. The 5a isoform, on the other hand, is not bone-derived and has been proposed to be a marker of activated macrophages and chronic inflammation. In this study, expression of TRAP protein and enzymatic activity in bone metastases from different primary sites was examined. TRAP activity was high in bone metastases from prostate cancer, intermediate in breast cancer, and low in lung and kidney cancers. The partially purified TRAP from breast cancer bone metastasis samples exhibited the enzymatic characteristics of purple acid phosphatase. Both 5a and 5b isoforms were expressed in bone metastases of different histogenetic origins, i.e. prostate, breast, lung and kidney, and also a novel previously unreported 42 kDa variant of the TRAP 5a isoform was identified in bone metastases. This novel TRAP 5a isoform was absent in human bone, indicating that the 42 kDa variant is specific to metastatic cancer tissue. Immunohistochemistry revealed that metastatic cancer cells were the predominant source of TRAP 5a, whereas tumor-associated macrophages and occasionally multinucleated giant cells in the tumor stroma preferentially expressed the proteolytically processed TRAP 5b variant. Our results indicate the presence of a previously unstudied variant of monomeric TRAP 5a in cancer cells, which may have functional and diagnostic implications. Moreover, the presence of TRAP-positive macrophages in bone metastases could, together with cancer cells and osteoclasts, contribute to the elevated levels of serum TRAP activity observed in patients with bone metastases.


Tartrate-resistant acid phosphatase Metastatic bone disease Macrophage Cancer Bone resorption Osteoclast 



Tartrate-resistant acid phosphatase




Bovine serum albumin


Fast protein liquid chromatography




Polyvinylidene fluoride



The authors thank Dr. Jussi Halleen for kindly providing the human recombinant TRAP. This work was supported by grants from the Swedish Research Council, Cancer-Allergy Foundation, Stockholm County Council (ALF) and Karolinska Institutet Research Funds.

Supplementary material

10585_2010_9358_MOESM1_ESM.tif (2.4 mb)
Supplementary Figure 1. Anti-monomeric TRAP immunostaining on primary breast cancer tissue sections gave strong signals in cancer cells in. Magnification ×40. (TIFF 2481 kb)


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Serhan Zenger
    • 1
  • Wentao He
    • 1
  • Barbro Ek-Rylander
    • 1
  • Daphne Vassiliou
    • 1
  • Rickard Wedin
    • 2
  • Henrik Bauer
    • 2
  • Göran Andersson
    • 1
  1. 1.Division of Pathology F 46, Department of Laboratory MedicineKarolinska Institute, Karolinska University HospitalHuddingeSweden
  2. 2.Oncology Service, Department of OrthopaedicsKarolinska University HospitalStockholmSweden

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