Concurrent Expression of CD47 and CD44 in Colorectal Cancer Promotes Malignancy
Concurrent Expression of CD47 and CD44 in Colorectal Cancer Promotes Malignancy
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DOI：
10.1159/000496027
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发表时间：
2019-01-01
期刊：
影响因子：
5
通讯作者：
Kuniyasu, Hiroki
中科院分区：
文献类型：
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作者：
Fujiwara-Tani, Rina;Sasaki, Takamitsu;Kuniyasu, Hiroki
CD47激活巨噬细胞表达的信号调节蛋白α并抑制其吞噬能力；因此，CD47 作为先天免疫系统中的免疫检查点而受到关注。人们认为癌症中 CD47 的表达可以使癌细胞逃避先天免疫系统的抗肿瘤免疫。在这项研究中，通过免疫染色检查结直肠癌 (CRC) 中 CD47 的表达，并与癌症干细胞标记物 CD44 的表达进行比较。在 95 例 II-IV 期 CRC 病例中，CD47 和 CD44 分别在 82 例和 80 例中表现出过度表达。两种表达水平均与远处转移相关。而且，各病例中CD47和CD44的表达均表现出显着的相关性。在III期病例中，CD47和CD44高表达病例的无病生存率比低表达病例差。此外，其中 3 名 IV 期病例接受了获得性免疫系统检查点抑制剂纳武单抗 (nivolumab) 治疗，2 名患者随后出现复发。所有复发肿瘤均高表达CD47和CD44，并表现出上皮间质转化（EMT）表型。我们的结果表明，CD47 促进结直肠癌的恶性程度，并与 EMT 相关，并增强癌细胞的干性。此外，我们的研究表明 CD47 和 CD44 参与赋予对程序性细胞死亡 (PD)-1/PD-配体 1 抑制剂的抗性。
CD47 activates signal regulatory protein alpha expressed on macrophages and suppresses its phagocytic ability; therefore, CD47 is drawing attention as an immune checkpoint in the innate immune system. Expression of CD47 in cancer is thought to allow cancer cells to escape antitumor immunity of the innate immune system. In this study, expression of CD47 was examined by immunostaining in colorectal cancer (CRC) and compared with the expression of CD44, which is a marker for cancer stem cells. In 95 cases of stage II-IV CRC, CD47 and CD44 showed overexpression in 82 and 80 cases, respectively. Both expression levels correlated with distant metastasis. Moreover, the expression of CD47 and CD44 in each case showed a significant correlation. In stage III cases, disease-free survival of cases showing high expression of CD47 and CD44 was worse than that of the cases with low expression. Furthermore, 3 of the stage IV cases were administered nivolumab, a checkpoint inhibitor of the acquired immune system, and 2 patients showed recurrence thereafter. All recurrent tumors highly expressed CD47 and CD44 and showed the epithelial-mesenchymal transition (EMT) phenotype. Our results suggest that CD47 promotes the malignancy of CRC in association with EMT and enhances the stemness of cancer cells. Moreover, our study suggests that CD47 and CD44 are involved in imparting resistance to programmed cell death (PD)-1/PD-ligand 1 inhibitors.