Prostate cancer metastases alter bone mineral and matrix composition independent of effects on bone architecture in mice — A quantitative study using microCT and Raman spectroscopy

Abstract Prostate cancer is the most common primary tumor and the second leading cause of cancer-related deaths in men in the United States. Prostate cancer bone metastases are characterized by abnormal bone remodeling processes and result in a variety of skeletal morbidities. Prevention of skeletal...

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Bibliographic Details
Published in:Bone (New York, N.Y.) N.Y.), 2013-10, Vol.56 (2), p.454-460
Main Authors: Bi, Xiaohong, Sterling, Julie A, Merkel, Alyssa R, Perrien, Daniel S, Nyman, Jeffry S, Mahadevan-Jansen, Anita
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bone and Bones - diagnostic imaging
Bone and Bones - metabolism
Bone Neoplasms - diagnostic imaging
Bone Neoplasms - metabolism
Bone Neoplasms - secondary
Bone quality
Fundamental and applied biological sciences. Psychology
Gynecology. Andrology. Obstetrics
Male
Male genital diseases
Medical sciences
Mice
Mice, SCID
Nephrology. Urinary tract diseases
Orthopedics
Osteolysis
Prostate cancer bone metastasis
Prostate cancer cells LNCaP C4-2B
Prostatic Neoplasms - complications
Prostatic Neoplasms - diagnostic imaging
Prostatic Neoplasms - metabolism
Radiography
Raman spectroscopy
Spectrum Analysis, Raman
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:Abstract Prostate cancer is the most common primary tumor and the second leading cause of cancer-related deaths in men in the United States. Prostate cancer bone metastases are characterized by abnormal bone remodeling processes and result in a variety of skeletal morbidities. Prevention of skeletal complications is a crucial element in prostate cancer management. This study investigated prostate cancer-induced alterations in the molecular composition and morphological structure of metastasis-bearing bones in a mouse model of prostate cancer using Raman spectroscopy and micro-computed tomography (microCT). LNCaP C4-2B prostate cancer cells were injected into the right tibiae of 5-week old male SCID mice. Upon sacrifice at 8 weeks post tumor inoculation, two out of the ten tumor-bearing tibiae showed only osteoblastic lesions in the radiographs, 4 osteolytic lesions only and 4 mixed with osteoblastic and osteolytic lesions. Carbonate substitution was significantly increased while there was a marked reduction in the level of collagen mineralization, mineral crystallinity, and carbonate:matrix ratio in the cortex of the intact tumor-bearing tibiae compared to contralateral controls. MicroCT analysis revealed a significant reduction in bone volume/total volume, trabecular number and trabecular thickness, as well as significant increase in bone surface/volume ratio in tibiae with osteolytic lesions, suggesting active bone remodeling and bone loss. None of the changes in bone compositional properties were correlated with lesion area from radiographs or the changes in bone architecture from microCT. This study indicates that LNCaP C4-2B prostate cancer metastases alter bone tissue composition independent of changes in architecture, and altered bone quality may be an important contributor to fracture risk in these patients. Raman spectroscopy may provide a new avenue of investigation into interactions between tumor and bone microenvironment.
ISSN:8756-3282
1873-2763
DOI:10.1016/j.bone.2013.07.006