Osteocytes serve as a progenitor cell of osteosarcoma.
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.
Department of Urology, University of Michigan, Ann Arbor, Michigan, 48109, USA.
Joseph L
JL
Sottnik
Brittany
B
Campbell
Rohit
R
Mehra
Omid
O
Behbahani-Nejad
Christopher L
CL
Hall
Evan T
ET
Keller
D000818:Animals; D001859:Bone Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D004285:Dogs; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology
C513309:DMP1 protein, human; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins
BONE; CANCER; DMP1; OSTEOCYTE; OSTEOSARCOMA