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.