ER阳性乳腺癌和ER阴性乳腺癌的癌干/祖细胞生物学行为比较

Comparion on the biological behavior of stem and progenitor cells derived from ER-positive breast cancer and ER-negative breast cancer

目的:探讨ER阳性乳腺癌和ER阴性乳腺癌的癌干/祖细胞生物学行为差异。方法:通过无血清培养方法获取富含乳腺癌癌干/祖细胞的非粘附乳腺球(mammospheres,MSs):体外无血清培养微球体细胞(mammospheres-derived cells,MSDCs)并绘制生长曲线,评价ER阳性乳腺癌和ER阴性乳腺癌MSDCs的增值能力;应用无血清连续克隆形成实验,计算MSDCs的MSs形成率(mammospheres forming efficiency,MSFE),比较两种MSDCs的自我更新能力;通过添加血清的培养方法诱导MSDCs分化,绘制生长曲线,比较两种MSDCs的分化能力:构建NOD/SCID小鼠模型,比较两种MSDCs移植瘤的生长差异。结果:ER阳性乳腺癌和ER阴性乳腺癌均能培养出MSs,ER阴性乳腺癌的MSs生长速度快,直径大,包含的细胞数量多;ER阴性乳腺癌的MSDCs具有更强的体外增殖能力、自我更新能力、分化能力和免疫缺陷动物体内致瘤能力。结论:ER阳性乳腺癌和ER阴性乳腺癌的癌干/祖细胞生物学行为存在明显的差异,两种类型的乳腺癌可能起源于不同的乳腺癌干/祖细胞。

Objective：To investigate the different biological behavior of ER-positive breast cancer and ER-negative breast cancer stem and progenitor cells derived from mammospheres.Method： The breast cancer stem and progenitor cells were enriched in suspension cultures as nonadherent mammospheres.The proliferative capacity of mammospheresderived cells（MSDCs）in serum-free media was assessed by determination growth curve.Serial clonal sphere formation assays were used to detect self-renewal capacity of MSDCs.The differentiation of MSDCs were induced by cultured them in media cotaining serum.The tumor formation ability of MSDCs was evaluated by implanting them into immune-deficient mice.Results： Cells isolated from ER-positive breast cancer and ER-negative breast cancer could grow in serum-free conditions as mammospheres.The mammospheres of ER-negative breast cancer grew faster,had a longer diameter and contained more cells than that of ER-positive breast cancer.The MSDCs of ER-negative breast cancer have greater proliferation capacity,self-renewal capacity,differentiation capacity in vitro and tumorigenicity in vivo compared to that of ER-positive breast cancer.Conclusion： The breast cancer stem and progenitor cells of ER-positive breast cancer and ER-negative have significantly different biological behavior and the two types of breast cancer may originate from different phenotype of stem and progenitor cells.