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2017 ; 7
(ä): 44824
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Alteration of osteoblast arrangement via direct attack by cancer cells: New
insights into bone metastasis
#MMPMID28303941
Kimura Y
; Matsugaki A
; Sekita A
; Nakano T
Sci Rep
2017[Mar]; 7
(ä): 44824
PMID28303941
show ga
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.