Quan Gerald M Y, Ojaimi Joseline, Nadesapillai A P Wijayanthi, Zhou Hong, Choong Peter F M
Department of Orthopaedics, University of Melbourne, St. Vincent's Hospital Melbourne, Melbourne, Vic., Australia.
Pathobiology. 2002;70(6):361-7. doi: 10.1159/000071277.
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.
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).
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.
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.
骨骺软骨是骨肉瘤侵袭的一道屏障，然而这种抗性背后的机制仍不清楚。本研究的目的是研究骨肉瘤生长的时间和空间模式以及对包括骨骺软骨在内的局部组织结构的侵袭情况。
我们使用骨肉瘤的体内小鼠模型，对疾病进展不同阶段的肿瘤进行组织学检查。我们将骨肉瘤穿透骨骺软骨的模式与两种强大的血管生成介质的表达模式进行了比较；促血管生成的血管内皮生长因子（VEGF）和抗血管生成的色素上皮衍生因子（PEDF）。
在所有检查的切片中，尽管肿瘤大小增加以及骨内和骨外破坏，但骨骺软骨在其整个长度上保持完整。在最晚期的病例中，只有生长板肥大区最下层的促血管生成层被侵蚀。这与高度表达血管生成因子VEGF的生长板层相对应。相比之下，静止层、增殖层和肥大上层在所有病例中均对骨肉瘤侵袭具有抗性。这与强效抗血管生成因子PEDF表达最高的层相对应。
骨骺软骨对骨肉瘤的局部侵袭具有抗性。受促血管生成和抗血管生成因子影响的血管生成平衡可能在这种抗性中起重要作用。
