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12 August 2017 : Laboratory Research  

Cancer-Associated Fibroblasts Autophagy Enhances Progression of Triple-Negative Breast Cancer Cells

Mengchuan Wang1ABCDEFG, Jian Zhang1BCD, Yizhe Huang1ABCDE, Shufeng Ji1AEG, Guoli Shao1AE, Shaobo Feng1B, Danxun Chen1B, Kankan Zhao1B, Zixiang Wang1B, Aiguo Wu1A*

DOI: 10.12659/MSM.902870

Med Sci Monit 2017; 23:3904-3912

Abstract

BACKGROUND: Cancer-associated fibroblasts (CAFs) are key factors in malignant tumor initiation, progression, and metastasis. However, the effect of CAFs autophagy on triple-negative breast cancer (TNBC) cells is not clear. In this study, the growth effect of TNBC cells regulated by CAFs autophagy was evaluated.

MATERIAL AND METHODS: CAFs were obtained from invasive TNBC tumors and identified by Western blot and immunofluorescence staining assay. CAFs were co-cultured with TNBC cells, and migration and invasion were evaluated by Matrigel-coated Transwell and Transwell inserts. TNBC cells growth was detected by MTT assay, and epithelial-mesenchymal transition (EMT) regulated by CAFs was evaluated by Western blot assay.

RESULTS: CAFs were identified by the high expression of α-smooth muscle actin (α-SMA) protein. Autophagy-relevant Beclin 1 and LC3-II/I protein conversion levels in CAFs were higher than those in NFs (P<0.05). TNBC cells migration, invasion, and proliferation levels were significantly improved in the CAFs-conditioned medium (CAFs-CM) group, compared with the other 3 groups (P<0.05). TNBC cells vimentin and N-cadherin protein levels were upregulated and E-cadherin protein level was downregulated in the CAFs-CM group compared with the control group (P<0.05). Further study indicated b-catenin and P-GSK-3β protein levels, which are the key proteins in the Wnt/β-catenin pathway, were upregulated in the CAFs-CM group compared with the control group (P<0.05).

CONCLUSIONS: Our data demonstrated CAFs autophagy can enhance TNBC cell migration, invasion, and proliferation, and CAFs autophagy can induce TNBC cells to engage in the EMT process through the Wnt/β-catenin pathway.

Keywords: Epithelial-mesenchymal transition, Triple Negative Breast Neoplasms

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750