Cancer-Associated Fibroblasts Correlate with Tumor-Associated Macrophages Infiltration and Lymphatic Metastasis in Triple Negative Breast Cancer Patients
Cancer-Associated Fibroblasts Correlate with Tumor-Associated Macrophages Infiltration and Lymphatic Metastasis in Triple Negative Breast Cancer Patients
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DOI：
10.7150/jca.28583
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发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Zhang, Wei-Jie
中科院分区：
文献类型：
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作者：
Zhou, Jing;Wang, Xiao-Hua;Zhang, Wei-Jie
背景资料：癌症相关成纤维细胞（CAFs）是肿瘤微环境中最重要的细胞之一，通过与其他类型的细胞相互作用，在加速肿瘤转移中发挥重要作用。肿瘤相关巨噬细胞（TAM）是主要的肿瘤浸润免疫细胞，在癌症进展中也起着重要作用。在这里，我们的目的是评估CAFs对三阴性乳腺癌（triple-negative breast cancer，TNBC）的TAM浸润和淋巴结转移的影响。材料和方法：本研究包括278例经组织学证实的TNBC患者。用α-平滑肌肌动蛋白和成纤维细胞活化蛋白的免疫组织化学染色鉴定CAFs。通过CD 163的表达检测浸润的TAM的极化功能状态。结果：CAFs相关标志物在具有侵袭行为（包括复发和组织分化差）的TNBC患者中表达更频繁。CAFs的高活化与TNBC患者中极化CD 163阳性TAM的浸润和淋巴结转移的增加呈正相关。多因素考克斯分析显示CAFs的活化、TAMs浸润和淋巴结转移是影响TNBC患者无病生存的独立预后因素。结论：肿瘤相关成纤维细胞与CD 163阳性巨噬细胞浸润和淋巴结转移相关，可能是TNBC患者潜在的预后预测因子。
Background: Cancer-associated fibroblasts (CAFs) have been shown to be among the most prominent cells in tumor microenvironment and play a significant role in accelerating tumor metastasis by interacting with other type of cells. Tumor-associated macrophages (TAMs), the predominant tumor-infiltrating immune cells, also play important roles in cancer progression. Here, we aimed to evaluate the effects of CAFs on infiltration of TAMs and lymphatic metastasis in triple-negative breast cancer (TNBC).Material and methods: The study included 278 patients with histologically confirmed TNBC. Immunohistochemical staining of alpha-smooth muscle actin and fibroblast activation protein were used to identify CAFs. Polarized functional status of infiltrated TAMs was detected by expression of CD163. The clinicopathological features were assessed from all the patients' medical records.Results: The CAFs-related markers were found to be expressed more frequently in TNBC patents with aggressive behaviors, including recurrence and poor histological differentiation. High activation of CAFs was positively correlated with elevated infiltration of polarized CD163-positive TAMs and lymph node metastasis in TNBC patients. Multivariate Cox analysis revealed that the activation of CAFs, TAMs infiltration, and lymph node metastasis were independent prognostic factors for disease-free survival in TNBC patients.Conclusion: Cancer-associated fibroblasts were associated with infiltration of CD163-positive macrophages and lymphatic metastasis, and may be potential prognostic predictors of TNBC.