1. Insights into the osteosarcoma microenvironment : multiscale analysis of structural and mineral heterogeneityFrancesca Rossi, Rydzyk Martyna Malgorzata, Luisa Barba, Emil Malucelli, Maria Elisabetta Federica Palamà, Chiara Gentili, Maddalena Mastrogiacomo, Alessia Cedola, Lucia Mancini, Murielle Salomè, Hiram Castillo Michel, Davide Maria Donati, Marco Gambarotti, Enrico Lucarelli, Michela Fratini, Stefano Iotti, 2025, izvirni znanstveni članek Povzetek: Osteosarcoma (OS) is a malignant and heterogeneous disease that typically originates in the long bones of children and adolescents. It is characterized by the presence of immature cells having an aggressive phenotype and rapid uncontrolled proliferation. OS progression induces significant molecular and cellular changes locally within the bone, resulting in the development of an abnormal tumor microenvironment (TME). The OS TME plays a crucial role in tumor progression and development, however, the precise effects of OS on bone structure and mineralization still remain poorly understood. In this study, we examined the OS TME by analyzing samples from osteoblastic, parosteal, and periosteal osteosarcomas. Employing advanced synchrotron-based X-ray techniques, we performed a multiscale analysis to evaluate the structural and mineral complexity of tumor-affected bone. Our results revealed marked morphological differences among the osteosarcoma subtypes, while con- firming that biomineralization remains active through the production of hydroxyapatite (HA). X-ray diffraction identified two distinct hydroxyapatite crystalline phases across all samples, suggesting a critical behavior of minerals in bone. Additionally, we observed that the bone mineral structure in periosteal and parosteal osteosarcomas exhibited crystal deformations along the c-axis, whereas the osteoblastic osteosarcoma displayed a mineral profile comparable to control bone. Micro-X-ray absorption near-edge spectroscopy revealed the occurrence of a dysregulated biomineralization in the parosteal and periosteal subtypes, marked by the presence of calcium compounds different from HA, in contrast to the mature mineral state found in the osteoblastic variant. These findings highlight the complexity of osteosarcoma repercussion on bone tissue, offering new in- sights into the interactions within the OS TME.
Ključne besede: osteosarcoma, biomineralization, XANES, synchrotron-based X-ray diffraction, X-ray computed microtomography
Objavljeno v DiRROS: 10.06.2025; Ogledov: 497; Prenosov: 403
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