Urist M R, Nakata N, Felser J M, Nogami H, Hanamura H, Miki T, Finerman G A
Clin Orthop Relat Res. 1977 May(124):251-66.
Histophysiology, ultrastructure, chemical analyses of transplants and implants of Dunn and Ridgway mouse osteosarcomas demonstrate that tumorigenesis is a manifestation of deranged morphogenesis in developing mesenchymal cell populations. The end product of development is defective, incompletely calcified, disorganized bone without any inclusions of bone marrow tissue. When Dunn osteosarcoma is freeze-dried and then implanted, the tumor is resorbed and replaced by deposits of normal cartilage, bone, and bone marrow. Freeze-dried Ridgway osteosarcoma is replaced only by a fibrous connective tissue scar. Disaggregated Dunn tumor osteoblasts synthesize a trypsin-labile collagenase-resistant cell surface localized bone morphogen. Tumor matrix stroma, prepared by sequential chemical extraction of soluble non-collagenous proteins also contains significant quantities of the same bone morphogen. Tumor tissue pulverized to particle size as small as 44 micrometer3 transmitted bone morphogen more rapidly than intact tumor tissue. The total tumor cell and stroma mediated bone morphogen produces three times more normal bone than normal cortical bone matrix. Our working hypothesis is that a normal bone morphogenetic polypeptide (BMP) is synthesized by Dunn osteosarcoma cells and retained by the tumor matrix stroma. Neither the mechanism of transmission nor the mesenchymal cell receptor sites of BMP are known.
邓恩和里奇韦小鼠骨肉瘤移植与植入物的组织生理学、超微结构及化学分析表明，肿瘤发生是发育中的间充质细胞群体形态发生紊乱的一种表现。发育的最终产物是有缺陷的、钙化不完全、结构紊乱的骨，且无任何骨髓组织内含物。当邓恩骨肉瘤经冷冻干燥后植入时，肿瘤会被吸收，代之以正常软骨、骨和骨髓的沉积。冷冻干燥的里奇韦骨肉瘤仅被纤维结缔组织瘢痕取代。离散的邓恩肿瘤成骨细胞合成一种对胰蛋白酶敏感、对胶原酶有抗性的细胞表面定位骨形态发生蛋白。通过依次化学提取可溶性非胶原蛋白制备的肿瘤基质也含有大量相同的骨形态发生蛋白。粉碎至粒径小至44立方微米的肿瘤组织比完整肿瘤组织更快传递骨形态发生蛋白。肿瘤细胞和基质介导的总骨形态发生蛋白产生的正常骨比正常皮质骨基质多两倍。我们的工作假设是，邓恩骨肉瘤细胞合成一种正常的骨形态发生多肽（BMP），并被肿瘤基质保留。BMP的传递机制和间充质细胞受体位点均未知。
