低氧条件下巨噬细胞分泌CCL22促进三阴乳腺癌转移

Macrophages Secreting CCL22 to Promote Triple-negative Breast Cancer Metastasis Under Hypoxia

三阴乳腺癌(Triple Negative Breast Cancer,TNBC)是乳腺癌中恶性程度最高的一种亚型,表现为很高的转移潜能。巨噬细胞,即肿瘤相关巨噬细胞(Tumor-Associated Macrophages,TAM),在促进TNBC转移中起了重要作用。乳腺癌作为一种实体肿瘤,往往处于缺氧环境中。低氧环境能够促进癌细胞的转移,然而低氧环境中巨噬细胞在促进肿瘤转移中的作用仍然不清楚。在该研究中,THP1细胞被诱导成TAM,经过缺氧培养后,通过Transwell实验检测其促进三阴乳腺癌细胞BT-549和MDA-MB-231的细胞迁移能力;通过尾静脉注射,将MDA-MB-231细胞移植于祼鼠体内,CT扫描,分析了TAM促进TNBC细胞的器官转移能力;通过ELISA实验检测低氧对TAM分泌的肿瘤转移相关因子的影响,通过GDSC在线软件分析了CCL22受体CCR4和其他CCR在乳腺癌组织与正常组织中表达的差异。结果表明低氧条件下巨噬细胞通过分泌CCL22的表达来促进三阴乳腺癌细胞迁移:经过缺氧培养后的TAM显著增强了TNBC细胞迁移能力,以及促进癌细胞在体内向肺转移;低氧诱导TAM分泌CCL22;CCL22受体CCR4在乳腺癌组织中的表达显著高于在正常组织中的。

Triple-negative breast cancer(TNBC)is the most malignant subtype of breast cancer and shows high metastatic potential.Macrophages(or known as tumor-associated macrophages,TAM)play an important role in promoting TNBC metastasis.Breast cancer as a solid tumor often exists in a hypoxic tumor microenvironment.Hypoxia promotes cancer cell metastasis,but the role of macrophages in promoting tumor metastasis in a hypoxic environment is still unclear.THP1 cells were differentiated into TAM and cultured in hypoxia.The migration ability of the TNBC cells BT-549 and MDA-MB-231 induced by TAM was detected through Transwell.MDA-MB-231 was transplanted through tail vein into the nude mice and the organ metastasis ability of TNBC cells induced by TAM was analyzed through CT scan.The effect of hypoxia on the secretion of several factors related to tumor metastasis in TAM was detected with the ELISA test.The difference between CCL22 receptor CCR4 and other CCR expression in breast cancer tissues and normal tissues was analyzed with the GDSC online software.The results showed that hypoxia-induced TAM significantly enhanced the migration of TNBC cells.Hypoxia induced CCL22 expression in TAM.Moreover,CCR4 expression in breast cancer tissues was significantly higher than that in normal tissues.In conclusion,TAM could promote the migration of TNBC cells through secretion of CCL22 under hypoxia.