Periostin is an
extracellular matrix protein that actively contributes to
tumor progression and
metastasis. Here, we hypothesized that it could be a marker of bone
metastasis formation. To address this question, we used two polyclonal
antibodies directed against the whole molecule or its C-terminal domain to explore the expression of intact and truncated forms of
periostin in the serum and tissues (lung, heart, bone) of wild-type and
periostin-deficient mice. In normal bones,
periostin was expressed in the periosteum and specific
periostin proteolytic fragments were found in bones, but not in soft tissues. In animals bearing osteolytic lesions caused by 4T1 cells, C-terminal intact
periostin (iPTN) expression disappeared at the invasive front of skeletal
tumors where bone-resorbing osteoclasts were present. In vitro, we found that
periostin was a substrate for osteoclast-derived
cathepsin K, generating proteolytic fragments that were not recognized by anti-
periostin antibodies directed against iPTN. In vivo, using an in-house sandwich immunoassay aimed at detecting iPTN only, we observed a noticeable reduction of serum
periostin levels (- 26%; P < 0.002) in animals bearing osteolytic lesions caused by 4T1 cells. On the contrary, this decrease was not observed in women with
breast cancer and bone
metastases when
periostin was measured with a human assay detecting total
periostin. Collectively, these data showed that mouse
periostin was degraded at the bone metastatic sites, potentially by
cathepsin K, and that the specific measurement of iPTN in serum should assist in detecting bone
metastasis formation in
breast cancer.