Hatano H, Tokunaga K, Ogose A, Hotta T, Yamagiwa H, Hayami T, Endo N, Takahashi H E
Department of Orthopedic Surgery, Niigata University School of Medicine, Japan.
J Pathol. 1998 Jun;185(2):204-11. doi: 10.1002/(SICI)1096-9896(199806)185:2<204::AID-PATH74>3.0.CO;2-E.
Osteosarcomas are malignant tumours producing osteoid and/or bone. It is difficult to distinguish tumour bone formation from reactive, based on their morphological features alone. The objective of this study was two-fold: to clarify the origins of bone-forming cells in human osteosarcoma transplanted into nude mice; and to examine the role of bone morphogenetic proteins (BMPs) in the tumour-induced osteogenesis. DNA in situ hybridization was carried out with digoxigenin (DIG) polymerase chain reaction (PCR) labelled DNA probes for human-specific 'Alu' and mouse-specific 'mouse L1 (m-L1)' genes. Human osteosarcoma cells, established cell lines of NOS-1, NOS-2, and HuO9, were transplanted separately into nude mice. Bone-forming cells of the bone in the NOS-1 or NOS-2 tumours were positive for Alu, while they were negative for m-L1. The cells lining the surface of trabeculae in the HuO9 tumour were positive for Alu, but a few of them were also positive for m-L1. The m-L1-positive cells expressed mouse osteocalcin and type 1 collagen mRNAs. These facts suggest that the mouse cells were involved in osteoid synthesis of the HuO9 tumour. The NOS-1 or NOS-2 tumours expressed human BMP 2-7 mRNAs, whereas the HuO9 tumour expressed human BMPs 2, 4, 5, and 7. The osteogenetic potential of the tumours may depend on the expression patterns of BMPs. These results demonstrate two distinct types of bone formation, by tumour cells and by an admixture of tumour and non-tumour cells. The present study showed that the HuO9 tumour produces chimeric bone formation. This is the first report to demonstrate the relationships between tumour cells and non-tumour cells in bone formation, using genetic markers.
骨肉瘤是产生类骨质和/或骨的恶性肿瘤。仅根据其形态特征很难区分肿瘤性骨形成和反应性骨形成。本研究有两个目的：阐明移植到裸鼠体内的人骨肉瘤中成骨细胞的来源；研究骨形态发生蛋白（BMPs）在肿瘤诱导成骨中的作用。使用地高辛（DIG）聚合酶链反应（PCR）标记的针对人特异性“Alu”和小鼠特异性“小鼠L1（m-L1）”基因的DNA探针进行DNA原位杂交。将人骨肉瘤细胞、NOS-1、NOS-2和HuO9的已建立细胞系分别移植到裸鼠体内。NOS-1或NOS-2肿瘤中骨的成骨细胞Alu呈阳性，而m-L1呈阴性。HuO9肿瘤中骨小梁表面的细胞Alu呈阳性，但其中少数细胞m-L1也呈阳性。m-L1阳性细胞表达小鼠骨钙素和I型胶原mRNA。这些事实表明小鼠细胞参与了HuO9肿瘤的类骨质合成。NOS-1或NOS-2肿瘤表达人BMP 2-7 mRNA，而HuO9肿瘤表达人BMPs 2、4、5和7。肿瘤的成骨潜能可能取决于BMPs的表达模式。这些结果证明了两种不同类型的骨形成，即肿瘤细胞形成的和肿瘤细胞与非肿瘤细胞混合形成的。本研究表明HuO9肿瘤产生嵌合性骨形成。这是首次使用遗传标记物证明骨形成中肿瘤细胞与非肿瘤细胞之间关系的报告。
