Yang Mei, Xu Juan, Wang Qi, Zhang An-Qin, Wang Kun
Department of Breast Cancer, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Department of Breast Cancer, Guangdong Women and Children's Hospital, Guangzhou, Guangdong 511400, P.R. China.
Oncol Lett. 2018 Mar;15(3):3918-3922. doi: 10.3892/ol.2018.7742. Epub 2018 Jan 8.
A genetically engineered strain that may be applied in the medically useful therapeutic strategy of using bacterial agents to target breast cancer in a tumor-bearing nude mouse model has been previously reported. Furthermore, immune cell accumulation in breast tumor types has been observed, particularly distributed in regions surrounding the bacteria. M2 macrophages are associated with breast cancer aggressiveness, whereas M1 macrophages are prone to devouring bacteria and killing cancer cells. Therefore, this engineered tumor-targeting salmonella strain was used in an attempt to reverse the phenotype of M2 macrophages into the M1 phenotype. Subsequent to the co-culture of M2 macrophages with the bacteria for a short time, >50% of the M2 macrophages were invaded by bacteria. These M2 macrophages exhibited a decreased expression of mannose receptor (an M2 phenotypic marker) and increased expression of human leukocyte antigen-antigen D related (an M1 phenotypic marker). The results of the present study indicated that differentiated M2 macrophages may be redirected into the M1 phenotype following exposure to the engineered bacteria stimulus. This effect may be a potential mechanism by which bacteria retard tumor growth. Thus, this engineered bacterium may be a useful candidate for targeting and redirecting M2 macrophages into the M1 phenotype.
先前已有报道称,一种基因工程菌株可应用于在荷瘤裸鼠模型中利用细菌制剂靶向乳腺癌的医学有用治疗策略。此外,已观察到乳腺肿瘤类型中有免疫细胞积聚,特别是分布在细菌周围区域。M2巨噬细胞与乳腺癌侵袭性相关,而M1巨噬细胞易于吞噬细菌并杀死癌细胞。因此,使用这种工程化的肿瘤靶向沙门氏菌菌株试图将M2巨噬细胞的表型逆转为M1表型。在M2巨噬细胞与细菌短期共培养后,超过50%的M2巨噬细胞被细菌侵袭。这些M2巨噬细胞表现出甘露糖受体(一种M2表型标志物)表达降低,而人类白细胞抗原-D相关抗原(一种M1表型标志物)表达增加。本研究结果表明,分化的M2巨噬细胞在受到工程化细菌刺激后可能会重定向为M1表型。这种效应可能是细菌延缓肿瘤生长的潜在机制。因此,这种工程化细菌可能是将M2巨噬细胞靶向并重定向为M1表型的有用候选物。