J Cancer 2018; 9(24):4635-4641. doi:10.7150/jca.28583

Research Paper

Cancer-Associated Fibroblasts Correlate with Tumor-Associated Macrophages Infiltration and Lymphatic Metastasis in Triple Negative Breast Cancer Patients

Jing Zhou1,7*, Xiao-Hua Wang2*, Yi-Xin Zhao3*, Cheng Chen4, Xin-Yun Xu5, Qi sun5, Hong-Yan Wu5, Ming Chen5, Jian-Feng Sang1, Lei Su1, Xiao-Qiao Tang1, Xian-Biao Shi1, Yin Zhang1, Qiao Yu6, Yong-Zhong Yao1,3✉, Wei-Jie Zhang1✉

1. Dept. of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China;
2. Dept. of Medical Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, China;
3. School of Medicine, Southeast University;
4. Dept. of Radiotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, China;
5. Dept. of Pathology, Affiliated Drum tower Hospital of Nanjing University Medical School, Nanjing, China;
6. Dept. of Breast Surgery, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, China;
7. Dept. of General Surgery, Kunshan Fourth People's Hospital, Suzhou, China
* Jing Zhou, Xiao-Hua Wang and Yi-Xin Zhao equally contributed to this study.

Abstract

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 α-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.

Keywords: triple-negative breast cancer, cancer-associated fibroblasts, tumor-associated macrophages, lymphatic metastasis, prognosis

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How to cite this article:
Zhou J, Wang XH, Zhao YX, Chen C, Xu XY, sun Q, Wu HY, Chen M, Sang JF, Su L, Tang XQ, Shi XB, Zhang Y, Yu Q, Yao YZ, Zhang WJ. Cancer-Associated Fibroblasts Correlate with Tumor-Associated Macrophages Infiltration and Lymphatic Metastasis in Triple Negative Breast Cancer Patients. J Cancer 2018; 9(24):4635-4641. doi:10.7150/jca.28583. Available from http://www.jcancer.org/v09p4635.htm