Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita, 879-5593, Japan.
Sci Rep. 2021 Sep 13;11(1):18099. doi: 10.1038/s41598-021-97153-2.
Interaction with surrounding healthy cells plays a major role in the growth and metastasis of osteosarcoma. In this study, we hypothesized that humoral factors, which do not require direct contact with cells, are involved in the interaction between osteosarcoma and the surrounding cells. We identified the humoral factor involved in the association between tumor cells and surrounding normal cells using a co-culture model and investigated the significance of our findings. When human osteosarcoma cells (MG63) and human mesenchymal stem cells (hMSCs) were co-cultured and comprehensively analyzed for changes in each culture group, we found that the expression of chemokine (CC motif) ligand 26 (CCL26) was significantly enhanced. We also analyzed the changes in cell proliferation in co-culture, enhanced interaction with administration of recombinant CCL26 (rCCL26), reduced interaction with administration of anti-CCL26 antibodies, changes in invasive and metastatic abilities. CCL26 levels, motility, and invasive capability increased in the co-culture group and the group with added rCCL26, compared to the corresponding values in the MG63 single culture group. In the group with added CCL26 neutralizing antibodies, CCL26 level decreased in both the single and co-culture groups, and motility and invasive ability were also reduced. In a nude mice lung metastasis model, the number of lung metastases increased in the co-culture group and the group with added rCCL26, whereas the number of tumors were suppressed in the group with added neutralizing antibodies compared to those in the MG63 alone. This study identified a possible mechanism by which osteosarcoma cells altered the properties of normal cells to favorably change the microenvironment proximal to tumors and to promote distant metastasis.
骨肉瘤的生长和转移与周围健康细胞的相互作用密切相关。在本研究中，我们假设无需与细胞直接接触的体液因子参与骨肉瘤与周围细胞的相互作用。我们使用共培养模型来鉴定肿瘤细胞与周围正常细胞相互作用涉及的体液因子，并探讨了我们研究结果的意义。当人骨肉瘤细胞（MG63）与人间充质干细胞（hMSC）共培养并对每个培养组的变化进行综合分析时，我们发现趋化因子（CC 基序）配体 26（CCL26）的表达显著增强。我们还分析了共培养中细胞增殖的变化、添加重组 CCL26（rCCL26）后增强的相互作用、添加抗 CCL26 抗体后相互作用减弱、侵袭和转移能力的变化。与 MG63 单独培养组相比，CCL26 水平、迁移和侵袭能力在共培养组和添加 rCCL26 的组中增加。在添加 CCL26 中和抗体的组中，无论是在单独培养还是共培养的组中，CCL26 水平均降低，迁移和侵袭能力也降低。在裸鼠肺转移模型中，与 MG63 单独组相比，共培养组和添加 rCCL26 的组中肺转移瘤的数量增加，而添加中和抗体的组中肿瘤数量减少。本研究确定了一种可能的机制，骨肉瘤细胞通过该机制改变正常细胞的特性，从而有利地改变肿瘤附近的微环境并促进远处转移。
