Liu Yonggang, Xiao Ailian, Zhang Biyuan
Department of Thoracic Oncology, Baotou Cancer Hospital Baotou 014000, Inner Mongolia, China.
Department of Respiratory and Critical Care Medicine, General Hospital of TISCO Taiyuan 030003, Shanxi, China.
Am J Transl Res. 2021 Nov 15;13(11):13135-13146. eCollection 2021.
Previous research has shown that CCR10 acts as a vital oncogene in the progression of multiple malignancies. However, its effect on the treatment of non-small-cell lung cancer (NSCLC) has not been investigated. Current research examined the effect of CCR10 on the cellular survival and migration of NSCLC, and the modulation of cell death and found that the expression levels of CCR10 and CCL27 (ligand) were highly upregulated in human NSCLC tissue and cell lines, A549 and H157, compared with adjacent normal lung specimens. MTT and colony formation assays revealed that the blockage of CCR10 inhibited the multiplication and survival of A549 and H157 cells. Further study showed that metastasis-relevant VEGF-C/D, MMP-2/9, TIMP-1/2 were also regulated via CCR10 activation. Notably, increased NF-κB levels were detected in cells with activated CCR10, whereas the levels of NF-κB decreased in cells with blocked CCR10. Finally, the recovery of NF-κB expression counteracted the suppressive influence of CCR10 blockage on NSCLC cell survival, migration, and invasion. These results improved our knowledge understanding the molecular mechanisms of CCR10-CCL27 in progression of NSCLC.
先前的研究表明，CCR10在多种恶性肿瘤的进展中起着至关重要的致癌基因作用。然而，其对非小细胞肺癌（NSCLC）治疗的影响尚未得到研究。当前的研究检测了CCR10对NSCLC细胞存活和迁移的影响以及对细胞死亡的调节作用，发现与相邻正常肺组织标本相比，CCR10和CCL27（配体）的表达水平在人NSCLC组织及细胞系A549和H157中高度上调。MTT和集落形成试验表明，阻断CCR10可抑制A549和H157细胞的增殖和存活。进一步研究表明，与转移相关的VEGF-C/D、MMP-2/9、TIMP-1/2也通过CCR10激活而受到调节。值得注意的是，在CCR10激活的细胞中检测到NF-κB水平升高，而在CCR10阻断的细胞中NF-κB水平降低。最后，NF-κB表达的恢复抵消了CCR10阻断对NSCLC细胞存活、迁移和侵袭的抑制作用。这些结果增进了我们对CCR10-CCL27在NSCLC进展中的分子机制的认识。
