Adipocyte-derived SFRP5 inhibits breast cancer cells migration and invasion through Wnt and epithelial-mesenchymal transition signaling pathways
| Autor: | Qinye Fu, Shuya Huang, Chunmiao Ye, Zhongbing Ma, Liyuan Liu, Liang Li, Yongjiu Wang, Zhigang Yu, Fei Zhou, Yujuan Xiang, Fei Wang, Lixiang Yu, Gengshen Yin, Wenzhong Zhou, Dezong Gao, Qiang Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
business.industry adipocytes EMT Wnt signaling pathway Adipokine Adipose tissue medicine.disease Metastasis chemistry.chemical_compound medicine.anatomical_structure Breast cancer Oncology chemistry breast cancer metastasis Adipocyte Cancer research Medicine Original Article Obesity Epithelial–mesenchymal transition SFRP5 skin and connective tissue diseases business Lymph node |
| Zdroj: | Chinese Journal of Cancer Research |
| ISSN: | 1993-0631 |
| DOI: | 10.21147/j.issn.1000-9604.2020.03.06 |
| Popis: | Objective Obesity is closely associated with metastasis in breast cancer patients. Secreted frizzled-related protein 5 (SFRP5), one of the novel adipokines with anti-inflammatory properties, is associated with obesity. This study aims to study the role of SFRP5 in the crosstalk between obesity and breast cancer metastasis and identify the underlying mechanism. Methods 3T3-L1 pre-adipocytes were differentiated to mature adipocytes and a hypertrophic adipocyte model was induced with palmitic acid (PA). Cell motility was measured in MDA-MB-231 and MCF-7 breast cancer cells co-cultured with adipocytes conditioned medium (CM) with or without SFRP5 protein. Wnt and epithelial-mesenchymal transition (EMT) signal pathways were investigated by western blot. Circulating SFRP5 level in 218 breast cancer patients and the association with clinicopathologic characteristics of breast cancer were further determined. Online databases ENCORI and PREDICT Plus were used to exam the link between SFRP5 and prognosis. Results Reduced SFRP5 level was detected in the hypertrophic adipocyte model. Recombinant SFRP5 protein inhibited MDA-MB-231 and MCF-7 cells invasion and migration induced by PA-treated adipocyte CM, and SFRP5 inhibition by specific antibody reversed the effect of SFRP5. Furthermore, SFRP5 significantly inhibited Wnt and downstream EMT in breast cancer cells. Low circulating SFRP5 level correlated with body mass index (BMI), lymph node (LN) metastasis, TNM stage and high Ki67 expression in breast cancer patients. Increased SFRP5 level was associated with favorable predicted survival. Kaplan-Meier curves showed high SFRP5 level in tumor tissue was associated with better outcome of breast cancer patients. Conclusions Our findings demonstrated SFRP5 is a vital adipokine that mediates the crosslink between obesity and the metastatic potential of breast cancer. Promotion of SFRP5 expression in the adipose microenvironment may represent a novel approach for preventing breast cancer metastasis. |
| Databáze: | OpenAIRE |
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