Decorin and chondroitin‐6 sulfate inhibit B16V melanoma cell migration and invasion by cellular acidification
Decorin and chondroitin‐6 sulfate inhibit B16V melanoma cell migration and invasion by cellular acidification
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DOI：
10.1002/jcp.22612
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发表时间：
2011-10
影响因子：
5.6
通讯作者：
C. Stock;O. Jungmann;D. Seidler
中科院分区：
文献类型：
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作者：
C. Stock;O. Jungmann;D. Seidler
在体内，细胞被嵌入到一个由多种细胞-细胞和细胞-基质相互作用产生和维持的环境中。转移到真皮的黑色素瘤细胞与细胞外基质(ECM)和成纤维细胞相互作用。为了研究细胞外基质成分和成纤维细胞在黑色素瘤(B16V)细胞迁移和侵袭中的作用，我们建立了由成纤维细胞及其富胶原基质和B16V细胞组成的共培养体系。B16V细胞和成纤维细胞之间的串扰表现为基质金属蛋白酶-2的释放和活性明显增加。时间推移显微镜显示，无论是核心蛋白聚糖还是硫酸软骨素，B16V细胞的迁移和侵袭能力都下降了50%以上。核心蛋白聚糖导致可逆的6-硫酸软骨素对B16V细胞不可逆的胞浆酸化。有趣的是，核心蛋白聚糖降低了NHE1的活性，而6-硫酸软骨素却没有。此外，粘附素和6-硫酸软骨素也酸化了细胞表面的pH，这可能会由于强烈的粘附性而阻止迁移。综上所述，目前的共培养体系是分析迁移、侵袭和释放基质金属蛋白酶的合适工具，这取决于细胞-基质的相互作用以及侵袭细胞和被其自制基质包围的细胞之间的串扰。我们展示了到目前为止未知的核心蛋白聚糖和软骨素-6-硫酸盐的功能：它们通过细胞内酸化抑制B16V细胞迁移的能力。J.细胞。物理。226：2641-2650,2011。©2010 Wiley-Liss公司。
In vivo, cells are embedded in an environment generated and maintained by multiple cell–cell and cell–matrix interactions. While transiting the dermis metastasizing melanoma cells interact with the extracellular matrix (ECM) and fibroblasts. To study the roles of ECM components and fibroblasts in melanoma (B16V) cell migration and invasion, we established a co‐culture system consisting of fibroblasts, their collagen‐rich matrix and B16V cells. The crosstalk between B16V cells and fibroblasts was indicated by a clear increase in release and activity of matrix‐metallo‐protease‐2. Time‐lapse microscopy revealed that in B16V cells exposed to either decorin or chondroitin sulfates migration and invasion decreased by more than 50%. Decorin led to a reversible, chondroitin‐6‐sulfate to an irreversible, cytosolic acidification of B16V cells. Interestingly, decorin lowered NHE1 activity whereas chondroitin‐6‐sulfate did not. Furthermore, decorin and chondroitin‐6‐sulfate also acidified the pH at the cell surface which might prevent migration due to strong adhesion. In conclusion, the present co‐culture system is an appropriate tool to analyze migration, invasion, and MMP release depending on cell–matrix interactions and the crosstalk between the invasive cells and those surrounded by their self‐made matrix. We show a so far unknown function of decorin and chondroitin‐6‐sulfate: their ability to inhibit B16V cell migration by intracellular acidification. J. Cell. Physiol. 226: 2641–2650, 2011. © 2010 Wiley‐Liss, Inc.