Sohara Yasuyoshi, Shimada Hiroyuki, Minkin Cedric, Erdreich-Epstein Anat, Nolta Jan A, DeClerck Yves A
Division of Hematology-Oncology, Department of Pediatrics, Keck School of Medicine, USA.
Cancer Res. 2005 Feb 15;65(4):1129-35. doi: 10.1158/0008-5472.CAN-04-2853.
The bone is the third most common site of cancer metastasis. To invade the bone, tumor cells produce osteoclast-activating factors that increase bone resorption by osteoclasts. Here we report that human neuroblastoma cells that form osteolytic lesions in vivo do not produce osteoclast-activating factors but rather stimulate osteoclast activity in the presence of human bone marrow mesenchymal stem cells. This alternative pathway of osteoclast activation involves a nonadhesive interaction between neuroblastoma cells and bone marrow mesenchymal stem cells. Stimulated bone marrow mesenchymal stem cells express markedly increased levels of interleukin-6, which is then responsible for osteoclast activation. This report describes a critical role of bone marrow mesenchymal stem cells in bone destruction in cancer.
骨骼是癌症转移的第三大常见部位。为了侵入骨骼，肿瘤细胞会产生破骨细胞激活因子，从而增加破骨细胞对骨的吸收。在此，我们报告称，在体内形成溶骨性病变的人神经母细胞瘤细胞不会产生破骨细胞激活因子，而是在人骨髓间充质干细胞存在的情况下刺激破骨细胞活性。这种破骨细胞激活的替代途径涉及神经母细胞瘤细胞与骨髓间充质干细胞之间的非黏附性相互作用。受到刺激的骨髓间充质干细胞表达的白细胞介素-6水平显著升高，进而导致破骨细胞激活。本报告描述了骨髓间充质干细胞在癌症骨破坏中的关键作用。
