title: Alteration of osteoblast arrangement via direct attack by cancer cells: New insights into bone metastasis.
abstract: Intact bone tissue exhibits a characteristic anisotropic microstructure derived from collagen fiber alignment and the related c-axis orientation of apatite crystals, which govern the mechanical properties of bone tissue. In contrast, tumor-invaded bone exhibits a disorganized, less-aligned microstructure that results in severely disrupted mechanical function. Despite its importance both in basic principle and in therapeutic applications, the classical understanding of bone metastasis is limited to alterations in bone mass regulated by metastatic cancer cells. In this study, we demonstrate a novel mechanism underlying the disruption of bone tissue anisotropy in metastasized bone. We observed that direct attack by cancer cells on osteoblasts induces the less-organized osteoblast arrangement. Importantly, the crystallographic anisotropy of bone tissue is quantitatively determined by the level of osteoblast arrangement. Osteoblast arrangement was significantly disrupted by physical contact with cancer cells such as osteolytic melanoma B16F10, breast cancer MDA-MB-231, and osteoblastic prostate cancer MDA-PCa-2b cells. The present findings demonstrate that the abnormal arrangement of osteoblasts induced by physical contact with cancer cells facilitates the disorganized microstructure of metastasized bone.
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Aira
authors.initials: A
authors.lastname: Matsugaki
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sekita
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000818:Animals; D015415:Biomarkers; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D002448:Cell Adhesion; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D015870:Gene Expression; D006801:Humans; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010014:Osteolysis; D011471:Prostatic Neoplasms / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D015415:Biomarkers