Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Huan-Hu-Xi Road, Tianjin 300060, China.
1] Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China [2] Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.
Br J Cancer. 2014 Feb 4;110(3):724-32. doi: 10.1038/bjc.2013.768. Epub 2013 Dec 12.
Cancer-associated fibroblasts (CAFs) activated by tumour cells are the predominant type of stromal cells in breast cancer tissue. The reciprocal effect of CAFs on breast cancer cells and the underlying molecular mechanisms are not fully characterised.
Stromal fibroblasts were isolated from invasive breast cancer tissues and the conditioned medium of cultured CAFs (CAF-CM) was collected to culture the breast cancer cell lines MCF-7, T47D and MDA-MB-231. Neutralising antibody and small-molecule inhibitor were used to block the transforming growth factor-β (TGF-β) signalling derived from CAF-CM, which effect on breast cancer cells.
The stromal fibroblasts isolated from breast cancer tissues showed CAF characteristics with high expression levels of α-smooth muscle actin and SDF1/CXCL12. The CAF-CM transformed breast cancer cell lines into more aggressive phenotypes, including enhanced cell-extracellular matrix adhesion, migration and invasion, and promoted epithelial-mesenchymal transition (EMT). Cancer-associated fibroblasts secreted more TGF-β1 than TGF-β2 and TGF-β3, and activated the TGF-β/Smad signalling pathway in breast cancer cells. The EMT phenotype of breast cancer cells induced by CAF-CM was reversed by blocking TGF-β1 signalling.
Cancer-associated fibroblasts promoted aggressive phenotypes of breast cancer cells through EMT induced by paracrine TGF-β1. This might be a common mechanism for acquiring metastatic potential in breast cancer cells with different biological characteristics.
肿瘤细胞激活的癌症相关成纤维细胞（CAFs）是乳腺癌组织中主要的基质细胞类型。CAFs 对乳腺癌细胞的相互影响及其潜在的分子机制尚未完全阐明。
从浸润性乳腺癌组织中分离基质成纤维细胞，并收集培养的 CAFs（CAF-CM）的条件培养基，用于培养乳腺癌细胞系 MCF-7、T47D 和 MDA-MB-231。使用中和抗体和小分子抑制剂阻断 CAF-CM 中源自转化生长因子-β（TGF-β）信号对乳腺癌细胞的影响。
从乳腺癌组织中分离的基质成纤维细胞具有 CAF 特征，α-平滑肌肌动蛋白和 SDF1/CXCL12 的表达水平较高。CAF-CM 将乳腺癌细胞系转化为更具侵袭性的表型，包括增强细胞-细胞外基质黏附、迁移和侵袭，并促进上皮-间充质转化（EMT）。癌症相关成纤维细胞分泌的 TGF-β1 多于 TGF-β2 和 TGF-β3，并激活乳腺癌细胞中的 TGF-β/Smad 信号通路。阻断 TGF-β1 信号可逆转 CAF-CM 诱导的乳腺癌细胞 EMT 表型。
通过旁分泌 TGF-β1 诱导 EMT，癌症相关成纤维细胞促进了乳腺癌细胞的侵袭表型。这可能是不同生物学特性的乳腺癌细胞获得转移潜能的共同机制。
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