TGF-β 在乳腺癌骨转移和原发灶中的过表达和 TGF-β 增强骨髓间充质干细胞中促癌转移细胞因子的表达。

TGF- Overexpression in Breast Cancer Bone Metastasis and Primary Lesions and TGF- Enhancement of Expression of Procancer Metastasis Cytokines in Bone Marrow Mesenchymal Stem Cells.

机构信息

Department of General Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, China.

Department of Internal Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, China.

出版信息

Biomed Res Int. 2018 Feb 8;2018:6565393. doi: 10.1155/2018/6565393. eCollection 2018.

Bone metastasis (BM) is the advanced complication of breast cancer, while bone marrow-derived mesenchymal stem cells (BMSCs) in the microenvironment unclearly contribute to cancer metastasis. This study investigated potential roles of transforming growth factor- (TGF-) in the interaction between breast cancer and BMSCs in BM. Clinical cases of breast cancer with bone metastasis (BMBC), breast cancer without bone metastasis (Non-BM-BC), and benign fibroadenoma (Benign) were enlisted in a retrospective study. TGF- was found obviously overexpressed in BM lesion of BMBC compared to primary lesion of both BMBC and Non-BM-BC ( < 0.01), and TGF- was higher in primary lesion of both BMBC and Non-BM-BC ( < 0.01) than Benign group. Interestingly, TGF- in nontumor tissues of both BMBC and Non-BM-BC was at a higher level than Benign group ( < 0.01), and numbers of macrophages in nontumor tissues of both BMBC and Non-BM-BC ( < 0.01) were higher than Benign group. Furthermore, in cultured human BMSCs, TGF- stimulated production of procancer cytokines including IL-6, VEGF, FGF10, FGF17, and TGF-1 in a dose-dependent manner. Thus, TGF- in BC could potentially be an important signal of carcinogenesis and metastasis. Macrophages in the nontumor tissue of BC may not be protective but could promote cancer metastasis.

骨转移（BM）是乳腺癌的晚期并发症，而骨髓来源的间充质干细胞（BMSCs）在微环境中对癌症转移的作用尚不清楚。本研究探讨了转化生长因子-（TGF-）β 在乳腺癌和 BMSCs 相互作用中的潜在作用及其在 BM 中的作用。本回顾性研究纳入了乳腺癌伴骨转移（BMBC）、无骨转移的乳腺癌（Non-BM-BC）和良性纤维腺瘤（Benign）的临床病例。结果发现，与 BMBC 的原发灶和 Non-BM-BC 的原发灶相比，BMBC 的 BM 病变中 TGF-β 明显过表达（<0.01），而 BMBC 和 Non-BM-BC 的原发灶中 TGF-β 水平高于良性组（<0.01）。有趣的是，BMBC 和 Non-BM-BC 的非肿瘤组织中的 TGF-β 水平高于良性组（<0.01），且 BMBC 和 Non-BM-BC 的非肿瘤组织中的巨噬细胞数量也高于良性组（<0.01）。此外，在培养的人 BMSCs 中，TGF-β 以剂量依赖性方式刺激包括 IL-6、VEGF、FGF10、FGF17 和 TGF-β1 在内的促癌细胞因子的产生。因此，BC 中的 TGF-β 可能是致癌和转移的重要信号。BC 非肿瘤组织中的巨噬细胞可能不是保护性的，而是可能促进癌症转移。