Resistance of epiphyseal cartilage to invasion by osteosarcoma is likely to be due to expression of antiangiogenic factors.
OBJECTIVE
Epiphyseal cartilage is a barrier to osteosarcoma invasion, however the mechanisms behind this resistance remain unclear. The aim of this study was to examine the chronological and spatial patterns of osteosarcoma growth and invasion of local tissue structures including epiphyseal cartilage.


METHODS
We used an in vivomouse model of osteosarcoma to histologically examine tumors at different stages of disease progression. We compared the pattern of osteosarcoma penetration of epiphyseal cartilage with the expression pattern of two potent mediators of angiogenesis; proangiogenic vascular endothelial growth factor (VEGF) and antiangiogenic pigment epithelium-derived factor (PEDF).


RESULTS
Epiphyseal cartilage remained intact across its entire length in all sections examined, despite increasing tumor size as well as intra- and extraosseous destruction. In the most advanced cases, only the proangiogenic lowermost layers of the hypertrophic zone of the growth plate were eroded. This corresponded with the growth plate layers which highly expressed the angiogenic factor VEGF. In contrast, the resting, proliferative and upper hypertrophic layers were resistant to osteosarcoma invasion in all cases. This corresponded to the layers with the highest expression of the potent antiangiogenic factor PEDF.


CONCLUSIONS
Epiphyseal cartilage is resistant to local invasion by osteosarcoma. The balance of angiogenesis, influenced by pro- and antiangiogenic factors, is likely to play an important role in this resistance.
Quan
Gerald M Y
GM
Department of Orthopaedics, University of Melbourne, St. Vincent's Hospital Melbourne, Melbourne, Vic., Australia.
Ojaimi
Joseline
J
Nadesapillai
A P Wijayanthi
AP
Zhou
Hong
H
Choong
Peter F M
PF
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005136:Eye Proteins; D006132:Growth Plate / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006614:Hindlimb; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000503:physiopathology; D009368:Neoplasm Transplantation; D009414:Nerve Growth Factors; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D011506:Proteins / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C467480:vascular endothelial growth factor A, mouse