Breast Cancer MCF-7 Cells Acquire Heterogeneity during Successive Co-Culture with Hematopoietic and Bone Marrow-Derived Mesenchymal Stem/Stromal Cells.

Breast Cancer MCF-7 Cells Acquire Heterogeneity during Successive Co-Culture with Hematopoietic and Bone Marrow-Derived Mesenchymal Stem/Stromal Cells.
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乳腺癌MCF-7细胞在与造血和骨髓间充质干细胞/基质细胞连续共培养过程中获得异质性

DOI:
10.3390/cells11223553
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发表时间:
2022-11-10
期刊:
影响因子:
6
通讯作者:
Pandol, Stephen J.
Pandol, Stephen J.
中科院分区:
生物学2区
文献类型:
--
作者:
Wang, Ruoxiang;Wang, Xudong;Yin, Liyuan;Yin, Lijuan;Chu, Gina Chia-Yi;Hu, Peizhen;Ou, Yan;Zhang, Yi;Lewis, Michael S.;Pandol, Stephen J.

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在疾病进展和骨转移过程中,乳腺肿瘤细胞与驻留在肿瘤微环境中的各种旁观者细胞相互作用。这种相互作用促进了肿瘤细胞的异质性。我们使用连续共培养作为实验模型来检测癌细胞与旁观者细胞的相互作用。用红色荧光蛋白标记的人乳腺癌MCF-7细胞的克隆RMCF7-2被跟踪观察形态、行为和基因表达的变化。RMCF7-2与不同类型的造血细胞共培养,在红色荧光细胞的悬浮生长中呈现稳定的圆形变化,由此衍生的克隆显示出明显的标志蛋白的表达变化,包括E-钙粘附素和雌激素受体α的减少,以及孕激素受体的丢失。在与骨髓间充质干细胞/基质细胞的连续共培养中,悬浮生长中的红色荧光克隆再次发生变化,采用贴壁生长,但形状多样。从第二轮共培养中恢复的红色荧光克隆在形态上是不同的,但保留了改变的标记蛋白表达,同时显示出更多的增殖、迁移和异种移植瘤形成。在连续共培养条件下,与旁观者细胞的相互作用导致细胞形态、生长行为和基因表达的永久性改变,为研究乳腺癌进展和转移过程中癌细胞的异质性提供了有力的模型。
During disease progression and bone metastasis, breast tumor cells interact with various types of bystander cells residing in the tumor microenvironment. Such interactions prompt tumor cell heterogeneity. We used successive co-culture as an experimental model to examine cancer–bystander cell interaction. RMCF7-2, a clone of the human breast cancer MCF-7 cells tagged with a red fluorescent protein, was tracked for morphologic, behavioral, and gene expression changes. Co-cultured with various types of hematopoietic cells, RMCF7-2 adopted stable changes to a rounded shape in suspension growth of red fluorescent cells, from which derivative clones displayed marked expressional changes of marker proteins, including reduced E-cadherin and estrogen receptor α, and loss of progesterone receptor. In a successive co-culture with bone marrow-derived mesenchymal stem/stromal cells, the red fluorescent clones in suspension growth changed once more, adopting an attachment growth, but in diversified shapes. Red fluorescent clones recovered from the second-round co-culture were heterogeneous in morphology, but retained the altered marker protein expression while displaying increased proliferation, migration, and xenograft tumor formation. Interaction with bystander cells caused permanent morphologic, growth behavioral, and gene expressional changes under successive co-culture, which is a powerful model for studying cancer cell heterogeneity during breast cancer progression and metastasis.
乳腺癌存活率由 ER/PR/HER2 亚型和根据肿瘤分级和免疫组织化学生物标志物的替代分类定义。
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