Multiscale characterization of the mineral phase at skeletal sites of breast cancer metastasis

• DOI: 10.1073/pnas.1708161114
• Publication Date: 2017-09-19T01:00:20Z
• Authors: Frank He; Aaron E. Chiou; Hyun Chae Loh; Maureen Lynch; Bo Ri Seo; Young Hye Song; Min Joon Lee; Rebecca Hoerth; Emely L. Bortel; Bettina M. Willie; Georg N. Duda; Lara A. Estroff; Admir Masic; Wolfgang Wagermaier; Peter Fratzl; Claudia Fischbach
• Keywords: Breast cancer metastasis; Characterization

Skeletal metastases, the leading cause of death in advanced breast cancer patients, depend on tumor cell interactions with mineralized bone extracellular matrix. Bone mineral is largely composed hydroxyapatite (HA) nanocrystals physicochemical properties that vary significantly by anatomical location, age, and pathology. However, it remains unclear whether regions typically targeted metastatic feature distinct HA materials properties. Here we combined high-resolution X-ray scattering analysis large-area Raman imaging, backscattered electron microscopy, histopathology, microcomputed tomography to characterize mouse models relevant skeletal locations. The proximal tibial metaphysis served as a common site our studies; identified disease-free bones this region contained smaller less-oriented relative ones constitute diaphysis. We further observed osteolytic metastasis led decrease nanocrystal size perfection remnant metaphyseal trabecular bone. Interestingly, model localized cancer, were also less perfect than corresponding controls. Collectively, these results suggest sites prone dissemination contain less-mature (i.e., smaller, less-perfect, crystals) primary tumors can increase immaturity even before secondary formation, mimicking alterations present during metastasis. Engineered recapitulating spatiotemporal dynamics will permit assessing functional relevance detected changes progression treatment