Bone serves as a transfer station for secondary dissemination of breast cancer

Metastasis is responsible for the majority of deaths among breast cancer patients.Although parallel polyclonal seeding has been shown to contribute to organ-specific metastasis,in the past decade,horizontal cross-metastatic seeding(metastasis-to-metastasis spreading)has also been demonstrated as a pattern of distant metastasis to multiple sites.Bone,as the most frequent first destination of breast cancer metastasis,has been demonstrated to facilitate the secondary dissemination of breast cancer cells.In this review,we summarize the clinical and experimental evidence that bone is a transfer station for the secondary dissemination of breast cancer.We also discuss the regulatory mechanisms of the bone microenvironment in secondary seeding of breast cancer,focusing on stemness regulation,quiescence-proliferation equilibrium regulation,epigenetic reprogramming and immune escape of cancer cells.Furthermore,we highlight future research perspectives and strategies for preventing secondary dissemination from bone.

小鼠动物模型中骨髓播散肿瘤细胞的检测方法

目的:探究小鼠骨髓中播散肿瘤细胞(disseminated tumor cells,DTCs)的检测方法。方法:采用慢病毒感染的方法构建MDA-MB-231-GFP/Luc乳腺癌细胞系,将MDA-MB-231-GFP/Luc细胞经左心室接种于NOD-SCID小鼠体内,构建骨髓DTCs小鼠模型。采用荧光定量RT-qPCR、流式细胞计数、骨组织连续切片免疫荧光染色三种检测方法对小鼠骨髓DTCs进行定量和组织学定位研究。结果:荧光定量RT-qPCR法和流式细胞计数法的检测下限分别为22个和25个绿色荧光蛋白阳性(GFP^(+))细胞。骨组织连续切片免疫荧光染色法虽然不能定量骨髓DTCs数量,但可观察到GFP^(+)DTCs在骨组织中的分布,定位于成骨细胞或骨基质附近。结论:三种检测方法联合使用可满足小鼠骨转移研究动物实验中骨髓DTCs的定量和定位研究的需求,可为乳腺癌骨转移和骨髓中休眠癌细胞研究提供方法学支持。