The C-Terminal Intact Forms of Periostin (iPTN) Are Surrogate Markers for Osteolytic Lesions in Experimental Breast Cancer Bone Metastasis

Evelyne Gineyts, Nicolas Bonnet, Cindy Bertholon, Marjorie Millet, Aurélie Pagnon-Minot, Olivier Borel, Sandra Geraci, Edith Bonnelye, Martine Croset, Ali Suhail, Cristina Truica, Nicholas Lamparella, Kim Leitzel, Daniel Hartmann, Roland Chapurlat, Allan Lipton, Patrick Garnero, Serge Ferrari, Philippe Clézardin, Jean Charles Rousseau

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)567-580
Number of pages14
JournalCalcified Tissue International
Volume103
Issue number5
DOIs
StatePublished - Nov 1 2018

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

Cite this

Gineyts, E., Bonnet, N., Bertholon, C., Millet, M., Pagnon-Minot, A., Borel, O., Geraci, S., Bonnelye, E., Croset, M., Suhail, A., Truica, C., Lamparella, N., Leitzel, K., Hartmann, D., Chapurlat, R., Lipton, A., Garnero, P., Ferrari, S., Clézardin, P., & Rousseau, J. C. (2018). The C-Terminal Intact Forms of Periostin (iPTN) Are Surrogate Markers for Osteolytic Lesions in Experimental Breast Cancer Bone Metastasis. Calcified Tissue International, 103(5), 567-580. https://doi.org/10.1007/s00223-018-0444-y