Osteocytes Serve as a Progenitor Cell of Osteosarcoma

ABSTRACT Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet t...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular biochemistry 2014-08, Vol.115 (8), p.1420-1429
Main Authors: Sottnik, Joseph L., Campbell, Brittany, Mehra, Rohit, Behbahani-Nejad, Omid, Hall, Christopher L., Keller, Evan T.
Format: Article
Language:English
Subjects:
Animals
BONE
Bone Neoplasms - etiology
Bone Neoplasms - metabolism
Bone Neoplasms - pathology
CANCER
Cell Differentiation - genetics
Cell Line, Tumor
DMP1
Dogs
Extracellular Matrix Proteins - biosynthesis
Extracellular Matrix Proteins - genetics
Gene Expression Regulation, Neoplastic
Humans
Mice
Osteoblasts - metabolism
Osteoblasts - pathology
OSTEOCYTE
Osteocytes - metabolism
Osteocytes - pathology
OSTEOSARCOMA
Osteosarcoma - etiology
Osteosarcoma - metabolism
Osteosarcoma - pathology
Phosphoproteins - biosynthesis
Phosphoproteins - genetics
Stem Cells - metabolism
Stem Cells - pathology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:ABSTRACT Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. Analysis of multiple murine, human, and canine OSA cell lines revealed DMP1 expression. To test the tumorigenic potential of osteocytes, MLO‐Y4, a SV‐40 immortalized murine osteocyte cell line, was injected into subcutaneous and orthotopic (intratibial) sites of mice. Tumor growth occurred in both locations. Orthotopic MLO‐Y4 tumors produced mixed osteoblastic/osteolytic radiographic lesions; a hallmark of OSA. Together, these data demonstrate for the first time that osteocytes can serve as OSA progenitors. J. Cell. Biochem. 115: 1420–1429, 2014. © 2014 Wiley Periodicals, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.24793