Analysis of the signal cross talk via CCL26 in the tumor microenvironment in osteosarcoma.
Analysis of the signal cross talk via CCL26 in the tumor microenvironment in osteosarcoma.
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DOI：
10.1038/s41598-021-97153-2
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发表时间：
2021-09-13
影响因子：
4.6
通讯作者：
Tsumura H
中科院分区：
文献类型：
--
作者：
Kawano M;Iwasaki T;Itonaga I;Kubota Y;Tanaka K;Tsumura H
骨肉瘤与周围健康细胞的相互作用在骨肉瘤的生长和转移中起重要作用。在本研究中，我们假设不需要与细胞直接接触的体液因子参与了骨肉瘤与周围细胞的相互作用。我们使用共培养模型确定了参与肿瘤细胞和周围正常细胞之间关联的体液因子，并研究了我们发现的意义。将人骨肉瘤细胞（MG63）与人间充质干细胞（hMSCs）共培养，综合分析各培养组的变化，我们发现趋化因子（CC motif）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、与重组CCL26 （rCCL26）的相互作用增强、与抗CCL26抗体的相互作用降低、侵袭和转移能力的变化。与MG63单一培养组的相应值相比，共培养组和添加rCCL26组的CCL26水平、运动性和侵袭能力均有所增加。在添加CCL26中和抗体组，CCL26水平在单培养组和共培养组均有所下降，运动性和侵袭能力也有所下降。在裸鼠肺转移模型中，共培养组和添加rCCL26组的肺转移数量增加，而添加中和抗体组的肿瘤数量受到抑制，与单独MG63组相比。本研究确定了一种可能的机制，通过这种机制，骨肉瘤细胞改变正常细胞的特性，有利于改变肿瘤近端微环境，促进远处转移。
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.
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